Pharmacotherapeutic potential of Vitis vinifera(grape) in age-related neurological diseases / Potencial farmacoterapéutico de Vitis vinifera(uva) en enfermedades neurológicas asociadas a la edad

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.

Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.

A longitudinal study of the progression of Huntington's disease and oropharyngeal dysphagia: A four-case follow-up

ABSTRACT Huntington's disease (HD) is a neurodegenerative disorder, with dysphagia being a common symptom of the disease. Few studies established a relationship between neuromotor impairment and dysphagia. There is also a lack of described therapeutic approaches for dysphagia in HD. This study aimed to better understand the progression of neurological clinical aspects, instrumental swallowing and dysphagia management in four patients presented with HD in an outpatient follow-up setting. The longitudinal follow-up period was 36 to 43 months through neuroclinical assessments (Unified Huntington's Disease Rating Scale) and fiberoptic endoscopic swallowing evaluations. Case 1 - a moderate decline of independence with safe swallowing. Case 2 - a moderate motor impairment, safe swallowing and moderate dysphagia during follow-up. Case 3 - a longer disease duration and increased motor impairment associated with moderate/severe dysphagia. Case 4 - a longer disease duration, need of assistance to perform daily activities, severe dysphagia and palliative care, considering the family decision of exclusive oral feeding. This longitudinal study revealed that the progression of neuromotor damage was not directly related to dysphagia development. This case series demonstrates the importance of follow-up settings with instrumental swallowing evaluations and careful consideration of early palliative care for HD patients.

Does the elbow position change the handgrip strength in Parkinson's disease? / A posição do cotovelo altera a força de preensão manual na doença de Parkinson?

Abstract The flexed elbow is a standardization position on the handgrip strength test, however the literature shows divergence in the values obtained from extended elbow. The aim of this study was to verify if there is such difference in people with Parkinson's disease. Cross-sectional study. Thirty-one elderly individuals with clinical diagnosis of Parkinson's disease, performed 2 handgrip tests, first with extended elbow and second with flexed elbow, with 48 hours of interval. There was not significantly different between positions for handgrip strength (p > 0.05). As well as, the effect size was insignificant (d < 0.19). The main results indicate there was no significant difference between the flexed and the extended protocol, the effect size was negative and very small, it shows there is no clinical effect. Since, there are no difference between elbow positions, The American Society of Hand Therapists standardized position is recommended for testing of handgrip strength.

Resumo O cotovelo flexionado é uma posição padronizada no teste de força de preensão manual, no entanto, a literatura mostra divergências nos valores obtidos com o cotovelo estendido. O objetivo deste estudo foi verificar se existe tal diferença em pessoas com a doença de Parkinson. Estudo transversal. Trinta e um idosos com diagnóstico clínico da doença de Parkinson realizaram 2 testes de preensão manual, o primeiro com o cotovelo estendido e o segundo com o cotovelo flexionado, com intervalo de 48 horas. Não houve diferença significativa entre as posições para a força de preensão manual (p > 0,05). Além disso, o tamanho do efeito foi insignificante (d < 0,19). Os principais resultados indicam que não houve diferença significativa entre o protocolo flexionado e o estendido, o tamanho do efeito foi negativo e muito pequeno, o que mostra que não há efeito clínico. Portanto, não há diferença entre as posições do cotovelo, recomenda-se a posição padronizada da Sociedade Americana de Terapeutas de Mão para o teste de força de preensão manual.

Investigación científica en el campo de las ataxias espinocerebelosas: una mirada bibliométrica

El objetivo del presente estudio consistió en caracterizar la producción científica relacionada con el campo de las ataxias espinocerebelosas, las cuales constituyen enfermedades neurodegenerativas, manifestadas por cuadros clínicos progresivos e invalidantes. La investigación es de tipo censal-documental y recupera metadatos de Scopus, correspondientes a 5654 investigaciones relacionadas con este problema de salud, durante el período 1961-2020. El procesamiento explora las principales características bibliométricas de los documentos publicados, el ritmo de crecimiento, la paternidad de las obras, el impacto por índice de citas, así como las redes de colaboración y la estructura que sigue el flujo del conocimiento. Se observa un despegue notable de la producción científica desde inicios de los años 90 del siglo pasado, coincidiendo con el desarrollo de investigaciones afines en el campo de la genética. También se constata un predominio en el estudio de los tipos SCA1, SCA2, SCA3, SCA6, y SCA17, donde los cuatro primeros corresponden a las ataxias de mayor prevalencia a escala mundial. El corpus documental refleja la consolidación de grupos de investigación relativamente estables, encabezados por líderes científicos y caracterizados por la ampliación sostenida de la colaboración internacional y por el trabajo colectivo e interdisciplinario. También se aprecia la tendencia hacia el aumento del número de referencias dentro de cada documento. Los mayores volúmenes productivos se concentran en países desarrollados, junto a países en vías de desarrollo donde existen elevados niveles de prevalencia en esta enfermedad.

The objective of the present study was to characterize the scientific production related to the field of spinocerebellar ataxias, which constitute neurodegenerative diseases, manifested by progressive and disabling clinical conditions. The research is census-documentary type and recovers metadata from Scopus, corresponding to 5,654 investigations related to this health problem, during the period 1961-2020. The processing explores the main bibliometric characteristics of the published documents, the pace of growth, the authorship of the works, the impact by citation index, as well as the collaboration networks and the structure that follows the flow of knowledge. A notable takeoff in scientific production has been observed since the beginning of the 90s of the last century, coinciding with the development of related research in the field of genetics. There is also a predominance in the study of the types SCA1, SCA2, SCA3, SCA6, and SCA17, where the first four correspond to the most prevalent ataxias worldwide. The documentary corpus reflects the consolidation of relatively stable research groups, headed by scientific leaders and characterized by the sustained expansion of international collaboration and collective and interdisciplinary work. There is also a trend towards increasing the number of references within each document. The largest productive volumes are concentrated in developed countries, along with developing countries where there are high levels of prevalence of this disease.

Mechanism of Traditional Chinese Medicine in Treatment of Neurodegenerative Diseases by Regulating Polarization Balance of Microglia： A Review / 中国实验方剂学杂志

Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

Therapeutic potential of NADH: in neurodegenerative diseases characterizde by mitochondrial dysfunction / 临床耳鼻咽喉头颈外科杂志

Nicotinamide adenine dinucleotide（NADH） in its reduced form of is a key coenzyme in redox reactions, essential for maintaining energy homeostasis.NADH and its oxidized counterpart, NAD+, form a redox couple that regulates various biological processes, including calcium homeostasis, synaptic plasticity, anti-apoptosis, and gene expression. The reduction of NAD+/NADH levels is closely linked to mitochondrial dysfunction, which plays a pivotal role in the cascade of various neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease.Auditory neuropathy（AN） is recognized as a clinical biomarker in neurodegenerative disorders. Furthermore, mitochondrial dysfunction has been identified in patients with mutations in genes like OPA1and AIFM1. However, effective treatments for these conditions are still lacking. Increasing evidence suggests that administratering NAD+ or its precursors endogenously may potentially prevent and slow disease progression by enhancing DNA repair and improving mitochondrial function. Therefore, this review concentrates on the metabolic pathways of NAD+/NADH production and their biological functions, and delves into the therapeutic potential and mechanisms of NADH in treating AN.

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases / 神经科学通报·英文版

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

Choreiform movements and basal ganglia calcification as a presentation of Fahr's disease

Basal ganglia calcifications may be a radiological finding in approximately 20% of the general population. When they are associated with neuropsychiatric and motor symptoms in an idiopathic form, they are known as Fahr's disease. They are termed "Fahr's syndrome" when they are secondary to an identifiable and potentially treatable cause. In this report, we present the clinical case of a 69-year-old woman with the onset of subacute chorea, with no other associated symptoms, in whom extensive basal ganglia calcifications were found on neuroimaging, due to which metabolic disorders were subsequently ruled out. The objective is to contribute to the characterization of the potential motor manifestations which would give rise to clinical suspicion. Due to its low incidence and the little information on this condition in the region, we want to encourage documentation of other cases and the process for ruling out other differential diagnoses, in order to obtain more information on its actual epidemiology and signs and symptoms in Colombia. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2635).

Efecto del compuesto N-2,6-dicloro-aralquil-2-Aminoindano en la conducta estereotipada de ratas. Acción dopaminérgica selectiva central sobre los ganglios basales más que en las estructuras límbicas / Effect of the compound N-2,6-dichloro-aralkyl-2-aminoindane on the stereotyped behavior of rats. Selective action on the central dopaminergic system in the basal ganglia over limbic structures

Resumen La dopamina 1, está implicada en trastornos neurodegenerativos que afectan al sistema nervioso central (SNC) tales como la enfermedad de Parkinson, entre otros. Aunque no se dispone aún de ningún fármaco capaz de prevenir, detener o curar la progresión de estas enfermedades, son numerosos los compuestos que han sido diseñados, sintetizados y evaluados farmacológicamente, que han aportado las generalizaciones farmacofóricas del receptor dopaminérgico, necesarias para la búsqueda de un fármaco capaz de mejorar o curar estas patologías. Los derivados 2-aminoindano-N-aralquílicos han mostrado tener actividad selectiva en el sistema dopaminérgico central, de modo tal que los compuestos clorhidratos de N-[(2,4-diclorofenil)-1-metil- etil]-2-aminoindano 2 y N-[(3,4-diclorofenil)-1-metil-etil]-2-aminoindano 3 demostraron tener actividad agonística mediada por mecanismos dopaminérgicos centrales. Con el propósito de contribuir en la búsqueda de nuevos fármacos que permitan restablecer la homeostasis de la transmisión dopaminérgica en la enfermedad de Parkinson, el compuesto N-2,6-dicloro-aralquil-2-aminoindano 4 fue diseñado a través de estrategias de la química medicinal, que contienen las aproximaciones farmacofóricas de los profármacos. La evaluación farmacológica del compuesto 4, en la conducta estereotipada en ratas macho de la cepa Sprague Dawley, demostró tener actividad agonística a través de la activación de los mecanismos dopaminérgicos centrales y mostró mayor selectividad en las respuestas de conductas estereotipadas propias de los ganglios basales sobre las respuestas conductuales propias de las estructuras límbicas.

Abstract Dopamine 1 is involved in neurodegenerative disorders affecting the central nervous system (CNS), such as Parkinson's disease. Despite the absence of some available drugs capable of preventing, stopping or curing the progression of such diseases, there are numerous compounds designed, synthesized, and pharmacologically tested which give rise to pharmacophoric generalizations about the dopaminergic receptor required for the search of a drug able to improve or cure those pathologies. N-aralkyl-2-aminoindane derivatives have shown selective activity in the central dopaminergic system. Both the N-[(2,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 2 and N-[(3,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 3 showed an agonistic activity mediated by central dopaminergic mechanisms. To contribute to the search of new drugs able to re-establish homeostasis in the dopaminergic transmission in Parkinson's disease, the compound N-2,6- dichloro-aralkyl-2-aminoindane 4 was designed through medicinal chemistry strategies that contain pharmacophoric approximations of prodrugs. The pharmacological evaluation of compound 4 in the stereotyped behavior of male Sprague Dawley rats showed agonistic activity through the activation of central dopaminergic mechanisms and a higher selectivity in the responses of stereo- typed behavior characteristic of the basal ganglia over the typical responses from limbic structures.

Sleep in the human aging process and circadian sleep rhythm disruptions / Sono no processo de envelhecimento humano e interrupções do ritmo circadiano do sono

The aging process is often related to sleeping difficulties, often due to changes in circadian rhythms. The circadian timing system is centered in the suprachiasmatic nucleus - the master biological clock - which synchronizes the rhythm of oscillators throughout the body, including the sleep-wake cycle. This affects the time, duration and quality of sleep according to the development and aging process, under external and internal influences. This review addresses the human circadian timing system, including endogenous and exogenous influences on circadian rhythms, their age-related particularities, as well as the repercussions of circadian misalignment in neurodegenerative diseases. Circadian rhythms naturally weaken with aging, but there are particularities according to age. Throughout life, sleep and circadian rhythm disorders are strongly bidirectionally related to the pathophysiology of some psychiatric and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This knowledge could potentially create valuable opportunities to improve the health of the world's population that is under circadian misalignment and aging.

O processo de envelhecimento está frequentemente relacionado a dificuldades de dormir, muitas vezes decorrentes de alterações nos ritmos circadianos. O sistema de ronometragem circadiana está centrada no núcleo supraquiasmático - o relógio biológico mestre - o qual sincroniza o ritmo dos osciladores em todo o corpo, incluindo o ciclo sono-vigília. Isso afeta o tempo, a duração e a qualidade do sono de acordo com o processo de desenvolvimento e envelhecimento, sob influências externas e internas. Esta revisão aborda o sistema de temporização circadiana humana, incluindo as influências endógenas e exógenas nos ritmos circadianos, suas particularidades relacionadas à idade, bem como as repercussões do desalinhamento circadiano nas doenças neurodegenerativas. Os ritmos circadianos enfraquecem naturalmente com o envelhecimento, mas há particularidades de acordo com a idade. Ao longo da vida, os transtornos do sono e do ritmo circadiano estão fortemente relacionados bidirecionalmente à fisiopatologia de algumas doenças psiquiátricas e neurodegenerativas, como as doenças de Alzheimer e Parkinson. Esse conhecimento pode potencialmente criar oportunidades valiosas para melhorar a saúde da população mundial que está sob desalinhamento circadiano e envelhecimento.

Resposta dos parâmentros do andar após intervenção com dicas auditivas rítmicas em idosos com doença de Parkinson / Response of gait parameters after intervention with rhythmic auditory cues in older people with parkinson's disease

Introdução: os comprometimentos do andar em idosos com doença de Parkinson (DP) estão associados à elevada ocorrência de quedas e à redução dos níveis de independência. O objetivo do estudo foi comparar a resposta dos parâmetros do andar em idosos com doença de Parkinson (DP), durante, imediatamente após e até uma hora após o término de uma sessão de treinamento do andar com e sem dicas auditivas rítmicas, utilizando três ritmos diferentes para o grupo dica (10% abaixo da cadência preferida, cadência preferida e 10% acima) e um ritmo diferente para o grupo controle (velocidade usual de cada participante). Métodos: vinte e nove idosos foram aleatoriamente distribuídos em dois grupos: "controle" e "dica". As sessões de intervenção tiveram 30 minutos de duração e a diferença entre os grupos foi a utilização de dicas auditivas rítmicas oferecidas por um metrônomo no grupo dica. O andar foi avaliado antes, durante e até uma hora após a sessão de intervenção. Resultados: os grupos apresentaram desempenhos similares ao longo das avaliações, com aumento do comprimento do passo e redução da variabilidade da duração do passo. Conclusão: a sessão de intervenção com dicas auditivas rítmicas apresentou efeitos similares aos da sessão de treino sem dica para o andar de idosos com DP.(AU)

Introduction: Gait impairments in older people with Parkinson's disease (PD) are associated with a high occurrence of falls and reduced levels of patients' independence. The objective of the study was to compare the response of gait parameters in older people with Parkinson's disease (PD), during, immediately after, and up to 1h after the end of a single locomotion training session with and without rhythmic auditory cues, using 3 different rhythms for the tip group (10% below the preferred cadence, preferred cadence and 10% above) and 1 different rhythm for the control group (usual speed of each participant). Materials and method: 29 older people were randomly assigned to two groups: Control and "Cue". The intervention sessions lasted 30 minutes and the difference between the groups was the use of rhythmic auditory cues offered by a metro-nome in the Cue group. Gait was assessed before, during, and up to 1 hour after the intervention session. Results: The groups showed similar performances throughout the assessments, with increased step length and reduced step time variability in response to the intervention (compared to the baseline assessment). Conclusion: The intervention session with rhythmic auditory cues had similar effects on gait as the session without cues in older people with PD.(AU)

Rita Levi-Montalcini: the neurologist who challenged fascism / Rita Levi-Montalcini: a neurologista que desafiou o fascismo

Abstract Rita Levi-Montalcini was a researcher in the field of neuroscience, Italian and Jewish in origin, who discovered the nerve growth factor and rightfully earned the 1986 Nobel Prize in Physiology or Medicine, alongside her collaborator Stanley Cohen. She was persecuted by the fascist dictatorship of Benito Mussolini and experienced gender and religious discrimination throughout her entire life. Despite these obstacles, she carried out her activities with diligence and grace, becoming a role model in the field. This paper reviews the life and career of Rita Levi-Montalcini.

Resumo Rita Levi-Montalcini foi uma pesquisadora no campo das neurociências, de origem Italiana e Judia, que descobriu o fator de crescimento neural e merecidamente recebeu o Prêmio Nobel de Fisiologia ou Medicina de 1986, em conjunto ao seu colaborador Stanley Cohen. Ela foi perseguida pela ditadura fascista de Benito Mussolini, e sofreu discriminação de gênero e religião durante sua vida inteira. A despeito desses obstáculos, sempre exerceu suas atividades com diligência e graça, tornando-se um exemplo nesse campo de estudo. O presente artigo faz uma revisão sobre a vida e carreira de Rita Levi-Montalcini.

Uso de cannabidiol para el control de síntomas refractarios en síndromes convulsivos y enfermedades neurodegenerativas / Use of cannabidiol for the control of refractory symptoms in convulsive syndromes and neurodegenerative diseases

Como parte de las terapias alternativas para el control de síntomas refractarios en enfermedades avanzadas destaca el uso de cannabidiol. Este se ha estudiado en patologías como enfermedad de Alzheimer, Parkinson y trastornos convulsivos. Los síndromes convulsivos están presentes en todos los grupos etarios. Dentro de este, la epilepsia es refractaria hasta en un 40 % de los pacientes, quienes han demostrado disminución en la frecuencia de convulsiones con el uso concomitante de cannabidiol y antiepilépticos convencionales, con efectos secundarios leves, como diarrea y somnolencia. Con el objetivo de determinar el uso del cannabidiol para el control de síntomas neurológicos refractarios en pacientes con síndromes convulsivos y enfermedades neurodegenerativas, se realizó una búsqueda bibliográfica en Pubmed, Scopus y Embase. Se incluyeron metaanálisis, artículos originales, revisiones sistemáticas y bibliográficas, y documentos de la Organización Panamericana de la Salud, publicados entre 2017 y 2022. Los efectos del cannabidiol lo convierten en una alternativa, adicional a la terapéutica convencional, para el control de síntomas en trastornos neurológicos, disminuyendo de forma sostenida el número total de episodios con un perfil de seguridad aceptable. Existe limitada información respecto al uso de cannabidiol en enfermedades neurodegenerativas, por lo que no se ha evidenciado su efectividad

As part of the alternative therapies for the control of refractory symptoms in advanced diseases, the use of cannabidiol stands out. It has been studied in pathologies such as Alzheimer's disease, Parkinson's disease, and convulsive disorders. Convulsive syndromes are present in all age groups. Within this group, epilepsy is refractory in up to 40 % of patients, who have shown a decrease in the frequency of seizures with the concomitant use of cannabidiol and conventional antiepileptics, with mild side effects such as diarrhea and drowsiness. To determine the use of cannabidiol for the control of refractory neurological symptoms in patients with seizure syndromes and neurodegenerative diseases, a literature search was performed in PubMed, Scopus, and Embase. Meta-analyses, original articles, systematic and literature reviews, and documents from the Pan American Health Organization, published between 2017 and 2022, were included. The effects of cannabidiol make it an alternative, in addition to conventional therapeutics, for symptom control in neurological disorders, sustainably decreasing the total number of episodes with an acceptable safety profile. There is limited information regarding the use of cannabidiol in neurodegenerative diseases, the reason its effectiveness has not been demonstrated.

Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review / Utilidade diagnóstica da estimulação magnética transcraniana para doenças neurodegenerativas: uma revisão crítica

ABSTRACT. Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.

RESUMO. As doenças neurodegenerativas representam desafio significativo por seu impacto na estrutura cerebral, função e cognição. À medida que a expectativa de vida aumenta, a prevalência dessas doenças cresce rapidamente, resultando em substanciais encargos pessoais, familiares e sociais. Esforços têm sido feitos para otimizar os processos diagnósticos e terapêuticos, com foco principal na caracterização clínica, cognitiva e de imagem. No entanto, o surgimento de técnicas de estimulação cerebral não invasivas, especificamente a estimulação magnética transcraniana (EMT), oferece compreensão funcional e potencial diagnóstico únicos. A TMS permite a avaliação direta da função cerebral, fornecendo informações valiosas inacessíveis por outros métodos. Esta revisão teve como objetivo resumir a utilidade diagnóstica atual e potencial da EMT na investigação de doenças neurodegenerativas, destacando sua relevância para o campo da neurociência cognitiva. As conclusões aqui apresentadas contribuem para o crescente corpo de investigação centrado na melhoria da nossa compreensão e gestão dessas condições debilitantes, particularmente em regiões com recursos limitados e necessidade premente de abordagens inovadoras.

Crossed aphasia in a left-handed patient with non-fluent variant of primary progressive aphasia with left asymmetric brain SPECT / Afasia cruzada em paciente canhota com afasia progressiva primária variante não fluente com SPECT cerebral assimétrico à esquerda

ABSTRACT Primary progressive aphasia is a clinical syndrome caused by neurodegeneration of areas and neural networks involved in language, usually in the left hemisphere. The term "crossed aphasia" denotes an acquired language dysfunction caused by a lesion in the ipsilateral hemisphere to the dominant hand. Objective: To describe a case of crossed aphasia in a 60-year-old left-handed patient with a non-fluent variant of primary progressive aphasia diagnosis (age of onset=52), evidenced by a left asymmetry on brain SPECT scan. Methods: Clinical and family history, the Edinburgh Handedness Inventory, Measurement of Functional Activities in Older Adults in the Community, the "Mini-Mental State Examination", the Trail Making Test, the Tower of London, and the Neuropsychological assessment for dementia, and neuroimaging studies were carried out. Results: Neuropsychological assessment showed severe cognitive impairment, especially regarding language. The magnetic resonance imaging showed important signs of cortico-subcortical atrophy, with predominance in the frontal and temporal lobes. The single-photon emission computed tomography scan showed moderate to severe hypoperfusion in the left cerebral hemisphere, including the hippocampus. Conclusion: We described a clinical case of crossed aphasia in a left-handed woman with a non-fluent variant of primary progressive aphasia with asymmetry on brain SPECT, mainly on the left, followed up for seven years.

RESUMO A afasia progressiva primária é uma síndrome clínica causada por uma neurodegeneração de áreas e redes neurais envolvidas na linguagem, geralmente no hemisfério esquerdo. O termo "afasia cruzada" denota uma disfunção adquirida de linguagem causada por uma lesão no hemisfério ipsilateral da mão dominante. Objetivo: Relatamos um caso de afasia cruzada em uma paciente de 60 anos, canhota, com um quadro clínico de afasia progressiva primária variante não fluente (idade de início=52), evidenciada por assimetria no SPECT cerebral à esquerda. Métodos: Foram realizados para o diagnóstico do caso: história clínica e familiar, o Inventário de Dominância de Edinburgh, a Escala de Atividades Funcionais de Pfeffer, o Miniexame do Estado Mental, o Teste das Trilhas, o Teste da Torre de Londres, a Avaliação Neuropsicológica Adequada às Demências e exames de neuroimagem. Resultados: A avaliação neuropsicológica mostrou comprometimento cognitivo severo, principalmente sobre a linguagem; a ressonância magnética do crânio mostrou sinais de involução córtico-subcortical, com predominância nos lobos frontal e temporal e a cintilografia cerebral por emissão de fóton único mostrou hipoperfusão moderada a severa no hemisfério cerebral esquerdo, incluindo o hipocampo. Conclusão: Registramos um caso clínico de afasia cruzada em uma paciente canhota com afasia progressiva primária variante não fluente com assimetria no SPECT cerebral, principalmente à esquerda, seguida há sete anos.

Cerebrospinal fluid evaluation as a diagnosis and prognosis tool: a bibliometric analysis of the 100 most cited articles / Avaliação do líquido cefalorraquidiano enquanto ferramenta diagnóstica e prognóstica: uma análise bibliométrica dos 100 artigos mais citados / Evaluación del líquido cefalorraquídeo como herramienta de diagnóstico y pronóstico: un análisis bibliométrico de los 100 artículos más citados

Introduction: Cerebrospinal fluid (CSF) analysis is critical in the diagnosis, prognosis, and treatment of a wide range of diseases, including multiple sclerosis, encephalitis, meningitis, brain tumors, Creutzfeldt-Jakob disease, Alzheimer's disease, and other neurodegenerative conditions. Objective: Bibliometric analysis of the 100 most cited articles to obtain deeper insights into the status of research in this sector, in order to provide support for evidence-based medicine (EBM). Methodology: The main collection of the Web of Science was used to collect relevant studies on the topic, and the VOSviewer software was employed to build bibliometric networks. The examination did not include materials from editorials, books, patents, or research with unspecified designs. The articles chosen are in the time range from 1991 to 2020. Results: It was noted that most of the articles were human observational studies focusing on the diagnosis of neurodegenerative diseases, specifically Alzheimer's, which were published in neurology and/or Alzheimer's-related journals, mainly in the United States of America. We discovered forward-looking research hotspots and trends in this domain, which can serve as an important guide to neurological research, generating subsidies for medical decision- making. Conclusion: The number of primary articles on the subject points to the need for further future research on CSF associated, mainly, with other neurodegenerative diseases, in addition to Alzheimer's, sustaining the diagnostic efficacy and EBM.

Introdução: A análise do líquido cefalorraquidiano (LCR) é fundamental no diagnóstico, prognóstico e tratamento de uma ampla gama de doenças, incluindo esclerose múltipla, encefalite, meningite, tumores cerebrais, doença de Creutzfeldt-Jakob, doença de Alzheimer e outras condições neurodegenerativas. Objetivo: Análise bibliométrica dos 100 artigos mais citados para obter insights mais aprofundados sobre o status da pesquisa nesse setor, a fim de fornecer subsídios para a medicina baseada em evidências (MBE). Metodologia: O acervo principal da Web of Science foi utilizado para coletar estudos relevantes sobre o tema, e o software VOSviewer foi empregado para construir redes bibliométricas. O exame não incluiu materiais de editoriais, livros, patentes ou pesquisas com desenhos não especificados. Os artigos escolhidos estão no intervalo de tempo de 1991 a 2020. Resultados: Observou-se que a maioria dos artigos eram estudos observacionais humanos com foco no diagnóstico de doenças neurodegenerativas, especificamente Alzheimer, que foram publicados em revistas de neurologia e/ou relacionadas ao Alzheimer, principalmente nos Estados Unidos da América. Descobrimos focos de pesquisa prospectivos e tendências nesse domínio, que podem servir como um importante guia para a pesquisa neurológica, gerando subsídios para a tomada de decisões médicas. Conclusão: O número de artigos primários sobre o tema aponta para a necessidade de novas pesquisas futuras sobre LCR associado, principalmente, a outras doenças neurodegenerativas, além da doença de Alzheimer, sustentando a eficácia diagnóstica e a BEM.

Introducción: El análisis del líquido cefalorraquídeo (LCR) es crítico en el diagnóstico, pronóstico y tratamiento de una amplia gama de enfermedades, incluyendo esclerosis múltiple, encefalitis, meningitis, tumores cerebrales, enfermedad de Creutzfeldt-Jakob, enfermedad de Alzheimer y otras afecciones neurodegenerativas. Objetivo: Análisis bibliométrico de los 100 artículos más citados para profundizar en el estado de la investigación en este sector, con el fin de dar soporte a la medicina basada en la evidencia (MBE). Metodología: Se utilizó la colección principal de la Web of Science para recopilar estudios relevantes sobre el tema, y se empleó el software VOSviewer para construir redes bibliométricas. El examen no incluyó materiales de editoriales, libros, patentes o investigaciones con diseños no especificados. Los artículos elegidos están en el rango de tiempo de 1991 a 2020. Resultados: Se observó que la mayoría de los artículos eran estudios observacionales en humanos centrados en el diagnóstico de enfermedades neurodegenerativas, específicamente Alzheimer, que fueron publicados en revistas de neurología y/o relacionadas con el Alzheimer, principalmente en los Estados Unidos de América. Descubrimos puntos calientes de investigación con visión de futuro y tendencias en este dominio, que pueden servir como una guía importante para la investigación neurológica, generando subsidios para la toma de decisiones médicas. Conclusión: El número de artículos primarios sobre el tema apunta a la necesidad de futuras investigaciones sobre el LCR asociadas, principalmente, con otras enfermedades neurodegenerativas, además del Alzheimer, manteniendo la eficacia diagnóstica y la MBE.

Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart. and Paullinia cupana Kunth

Abstract Acai (Euterpe oleracea Mart.) and guarana (Paullinia cupana Kunth) are native species from the Amazon Forest that in folk medicine are used to treat several diseases due to their anti-inflammatory and antioxidant properties. This review brings together findings from different studies on the potential neuroprotective effects of acai and guarana, highlighting the importance of the conservation and sustainable exploitation of the Amazon Forest. A bibliographic survey in the PubMed database retrieved indexed articles written in English that focused on the effects of acai and guarana in in vitro and in vivo models of neurodegenerative diseases. In general, treatment with either acai or guarana decreased neuroinflammation, increased antioxidant responses, ameliorated depression, and protected cells from neurotoxicity mediated by aggregated proteins. The results from these studies suggest that flavonoids, anthocyanins, and carotenoids found in both acai and guarana have therapeutic potential not only for neurodegenerative diseases, but also for depressive disorders. In addition, acai and guarana show beneficial effects in slowing down the physiological aging process. However, toxicity and efficacy studies are still needed to guide the formulation of herbal medicines from acai and guarana.

Enterovirus infection and its relationship with neurodegenerative diseases

Neurodegenerative diseases (NDs) are increasingly common, especially in populations with higher life expectancies. They are associated mainly with protein metabolism and structure changes, leading to neuronal cell death. Viral infections affect these cellular processes and may be involved in the etiology of several neurological illnesses, particularly NDs. Enteroviruses (EVs) frequently infect the central nervous system (CNS), causing neurological disease. Inflammation, disruption of the host autophagy machinery, and deregulation and accumulation/misfolding of proteins are the main alterations observed after infection by an EV. In this perspective, we discuss the most recent findings on the subject, examining the possible role of EVs in the development of NDs, and shedding light on the putative role played by these viruses in developing NDs.

Intervention of next-generation sequencing in diagnosis of Alzheimer's disease: challenges and future prospects / Intervenção do sequenciamento de nova geração no diagnóstico da doença de Alzheimer: desafios e perspectivas futuras

ABSTRACT Clinical diagnosis of several neurodegenerative disorders based on clinical phenotype is challenging due to its heterogeneous nature and overlapping disease manifestations. Therefore, the identification of underlying genetic mechanisms is of paramount importance for better diagnosis and therapeutic regimens. With the emergence of next-generation sequencing, it becomes easier to identify all gene variants in the genome simultaneously, with a system-wide and unbiased approach. Presently various bioinformatics databases are maintained on discovered gene variants and phenotypic indications are available online. Since individuals are unique in their genome, evaluation based on their genetic makeup helps evolve the diagnosis, counselling, and treatment process at the personal level. This article aims to briefly summarize the utilization of next-generation sequencing in deciphering the genetic causes of Alzheimer's disease and address the limitations of whole genome and exome sequencing.

RESUMO O diagnóstico clínico de vários distúrbios neurodegenerativos com base no fenótipo clínico é difícil devido à sua natureza heterogênea e às manifestações da doença que se sobrepõem. Portanto, a identificação dos mecanismos genéticos subjacentes é de suma importância para um melhor diagnóstico e regimes terapêuticos. Com o surgimento do sequenciamento de próxima geração, o diagnóstico se tornou mais acessível com uma abordagem imparcial em todo o sistema para identificar simultaneamente todas as variantes de genes no genoma. Atualmente, vários bancos de dados de bioinformática sobre variantes genéticas descobertas e indicações fenotípicas estão disponíveis online. Uma vez que os indivíduos são únicos em seu genoma, a avaliação com base em sua composição genética ajudou na evolução do processo de diagnóstico, aconselhamento e tratamento em nível pessoal. Este artigo teve como objetivo resumir brevemente a utilização do sequenciamento de próxima geração para decifrar as causas genéticas da doença de Alzheimer (DA) e abordar as limitações do sequenciamento completo do genoma e do exoma.

Nanopolyphenol rejuvenates microglial surveillance of multiple misfolded proteins through metabolic reprogramming

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.