Progress on the role of Kalirin-7 in exercise intervention-mediated improvement of neurodegenerative diseases / 生理学报

Guanine nucleotide exchange factor Kalirin-7 (Kal-7) is a key factor in synaptic plasticity and plays an important regulatory role in the brain. Abnormal synaptic function leads to the weakening of cognitive functions such as learning and memory, accompanied by abnormal expression of Kal-7, which in turn induces a variety of neurodegenerative diseases. Exercise can upregulate the expression of Kal-7 in related brain regions to alleviate neurodegenerative diseases. By reviewing the literature on Kal-7 and neurodegenerative diseases, as well as the research progress of exercise intervention, this paper summarizes the role and possible mechanism of Kal-7 in the improvement of neurodegenerative diseases by exercise and provides a new rationale for the basic and clinical research on the prevention and treatment of neurodegenerative diseases by exercise.

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders / 神经科学通报·英文版

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Light therapy: a new option for neurodegenerative diseases / 中华医学杂志(英文版)

Given the increasing incidence of neurodegenerative disease (ND), recent research efforts have intensified the search for curative treatments. Despite significant research, however, existing therapeutic options for ND can only slow down the progression of the disease, but not provide a cure. Light therapy (LT) has been used to treat some mental and sleep disorders. This review illustrates recent studies of the use of LT in patients with ND and highlights its potential for clinical applications. The literature was collected from PubMed through June 2020. Selected studies were primarily English articles or articles that could be obtained with English abstracts and Chinese main text. Articles were not limited by type. Additional potential publications were also identified from the bibliographies of identified articles and the authors' reference libraries. The identified literature suggests that LT is a safe and convenient physical method of treatment. It may alleviate sleep disorders, depression, cognitive function, and other clinical symptoms. However, some studies have reported limited or no effects. Therefore, LT represents an attractive therapeutic approach for further investigation in ND. LT is an effective physical form of therapy and a new direction for research into treatments for ND. However, it requires further animal experiments to elucidate mechanisms of action and large, double-blind, randomized, and controlled trials to explore true efficacy in patients with ND.

Observations from a nationwide vigilance program in medical care for spinal muscular atrophy patients in Chile / Atrofia muscular espinal en Chile, resultados de un programa de atención médica nacional

ABSTRACT Spinal muscular atrophy (SMA) has gained much attention in the last few years because of the approval of the first intrathecal treatment for this neurodegenerative disease. Latin America needs to develop the demographics of SMA, timely access to diagnosis, and appropriate following of the standards of care recommendations for patients. These are essential steps to guide health policies. Methods This was a descriptive study of a cohort of SMA patients from all over Chile. We analyzed the clinical, motor functional, and social data, as well as the care status of nutritional, respiratory and skeletal conditions. We also measured the SMN2 copy number in this population. Results We recruited 92 patients: 50 male; 23 SMA type-1, 36 SMA type-2 and 33 SMA type-3. The median age at genetic diagnosis was 5, 24 and 132 months. We evaluated the SMN2 copy number in 57 patients. The SMA type-1 patients were tracheostomized and fed by gastrostomy in a 69.6 % of cases, 65% of SMA type-2 patients received nocturnal noninvasive ventilation, and 37% of the whole cohort underwent scoliosis surgery. Conclusion Ventilatory care for SMA type-1 is still based mainly on tracheostomy. This Chilean cohort of SMA patients had timely access to genetic diagnosis, ventilatory assistance, nutritional support, and scoliosis surgery. In this series, SMA type-1 is underrepresented, probably due to restrictions in access to early diagnosis and the high and early mortality rate.

La Atrofia Muscular Espinal (AME) ha concitado mucha atención en los últimos 2 años debido a la aprobación del primer tratamiento intratecal para esta enfermedad neurodegenerativa. América Latina necesita desarrollar la demografía de AME, un acceso oportuno al diagnóstico y un seguimiento apropiado de los pacientes que incorporen los estándares de atención recomendados por expertos. Estos son pasos esenciales para orientar las futuras políticas de salud en esta enfermedad. Métodos Este es un estudio descriptivo de una cohorte de pacientes con AME de todo el país. Se analizaron los datos clínicos, motores, funcionales, sociales y el estado nutricional, respiratorio y esquelético de los pacientes. También medimos el número de copias del gen SMN2 en esta población. Resultados se reclutaron 92 pacientes, 50 varones; 23 AME tipo 1, 36 AME tipo 2 y 33 AME tipo 3. La edad media al diagnóstico genético fue de 5, 24 y 132 meses respectivamente. Evaluamos el número de copias de SMN2 en 57 pacientes. Un 69,6% de los pacientes con AME tipo 1 estaban traqueostomízados y gastrostomizados , un 65% de los pacientes con AME tipo 2 usaban ventilación nocturna no invasiva y el 37% de toda la cohorte presentaba una cirugía de escoliosis. Conclusión Esta cohorte chilena de pacientes con AME tuvo acceso oportuno al diagnóstico genético, asistencia ventilatoria, apoyo nutricional y cirugía de escoliosis, sin embargo, la atención ventilatoria para AME tipo 1 continúa aun basándose principalmente en la traqueostomía. En esta serie, AME tipo 1 está subrepresentada, probablemente debido a las restricciones en el acceso al diagnóstico temprano y la tasa de mortalidad alta y temprana.

Violência e sofrimento social no itinerário de travestis de Santa Maria, Rio Grande do Sul, Brasil / Violence and social distress among transgender persons in Santa Maria, Rio Grande do Sul State, Brazil / La violencia y el sufrimiento social en el itinerario de las personas transgénero de Santa María, Río Grande do Sul, Brasil

No ano de 2012, realizamos pesquisa etnográfica com travestis de Santa Maria, Rio Grande do Sul, Brasil, por meio de observação participante, entrevistas e acompanhamento de suas vidas cotidianas. Durante esse período, percebemos que as violências física e simbólica e o sofrimento delas decorrentes eram invariantes, condição com a qual tinham que lidar em seus itinerários, em suas práticas e afazeres diários. Este artigo discute as violências vivenciadas nas trajetórias percorridas pelas travestis (família, escola, delegacias, serviços de saúde), procurando, sobretudo, compreender como tais violências estão relacionadas às experiências nos serviços de saúde e como os serviços de saúde por elas acessados reagiram às violências.

The authors conducted an ethnographic research with transgender persons in Santa Maria, Rio Grande do Sul State, Brazil, in 2012, using participant observation, semi-structured interviews, and following their everyday lives. These individuals invariably experienced physical and symbolic violence and the resulting distress, a condition they had to deal with in their careers and daily practices and tasks. The article discusses the violence experienced by transvestites (in the family, school, police precincts, and health services), specifically seeking to understand how such violence relates to their experiences with health services and how the latter respond.

Hemos llevado a cabo una investigación etnográfica con personas transgénero de Santa María, Río Grande do Sul, Brasil, durante el año 2012, a través de la observación participante, entrevistas semiestructuradas y seguimiento de su vida cotidiana. Durante este período, se observó que la violencia física y simbólica y el sufrimiento que resulta de ellos, eran invariables, una condición que tenían que hacer frente en sus carreras, en sus prácticas y actividades diarias. Este artículo describe el panorama de la violencia experimentada en la rutina de transexuales (familia, escuela, policía, servicios de salud), con el objetivo particular de entender cómo este tipo de violencia está relacionado con experiencias en el cuidado de la salud y cómo los servicios de salud reaccionaron a este tipo de situaciones de violencia.

Virtual reality in physical rehabilitation of patients with Parkinson's disease

INTRODUCTION: The Virtual Reality (VR) can be a therapeutic tool used in neurorehabilitation field. It is considered a ludic activity that provides visual and auditory feedbacks, facilitating the patients' adherence to treatment. AIMS: To perform literature review about influences of VR in rehabilitation of patients with Parkinson's disease. METHODS: Data banks were used from the following virtual libraries: Medline, PEDro, Lilacs, Scielo and PubMed using the following keywords: Parkinson's disease and Virtual Reality; Parkinson's disease and Wii as well as analogous keywords in Spanish and Portuguese to obtain the scientific papers. PEDro scale was used to analyze the methodological quality of the papers. RESULTS: From fifty papers obtained after inclusion and exclusion criteria were retained 16 papers to analyses. According to PEDro scale most of the papers had low score. The results suggest that VR shows positive aspects in velocity and movement time, balance, gait, postural control and functionality of upper extremities. The ludic activity provided by VR and the contribution of visual and auditory feedbacks of this intervention can be the great potential of this new tool. CONCLUSION: The VR is useful to make potent: motor control, functionality, cognitive capacity and balance, but still need more scientific studies with methodological qualities to confirm the results of the VR in Parkinson's disease...

INTRODUÇÃO: A realidade virtual (RV) pode ser uma ferramenta terapêutica utilizada no campo da neurorreabilitação. É considerada uma atividade lúdica que fornece feedback visual e auditivo, facilitando a adesão dos pacientes ao tratamento. OBJETIVO: Realizar uma revisão de literatura a respeito da influência da RV na reabilitação de pacientes com doença de Parkinson. Método: Utilizamos como base de dados os sistemas virtuais das bibliotecas Medline, PEDro, Lilacs, Scielo e Pubmed, a partir dos seguintes descritores: Doença de Parkinson e Realidade Virtual; Doença de Parkinson e Wii e seus equivalentes em espanhol e inglês para obtenção dos artigos. Foi utilizada a escala PEDro para fins de pontuação metodológica dos artigos analisados. RESULTADOS: A partir de 50 artigos obtidos após a aplicação dos critérios de inclusão e exclusão, foram obtidos 16 artigos para análise. De acordo com a escala PEDro a maioria dos artigos teve baixa pontuação. Os resultados sugerem que a RV apresenta resultados positivos nas variáveis velocidade e tempo de movimento, equilíbrio, marcha, controle postural e funcionalidade de membros superiores. A atividade lúdica oferecida pela RV e a contribuição dos feedbacks visual e auditivo oferecido por este tipo de intervenção podem ser o grande potencial desta nova ferramenta. CONCLUSÃO: A RV é útil na potencialização do controle motor, na funcionalidade, na capacidade cognitiva e no equilíbrio, mas ainda precisa de estudos com melhor qualidade metodológica para confirmação dos resultados da RV na doença de Parkinson...

Neuropatogenia de HIV en la era HAART / Neuropathogenesis of HIV in the HAART era

La infección de tejidos cerebrales por HIV se asocia a desórdenes neurocognitivos identificados bajo la denominación HAND y categorizados en demencia, formas moderadas y formas asintomáticas. La introducción de terapia de alta efectividad ha implicado un notorio descenso de la demencia, pero no ha influido sobre las formas moderadas y asintomáticas que afectan alrededor del 50% de los pacientes bajo tratamiento. Esa disfunción cognitiva resulta de la pérdida de neuronas que, sin embargo, no han sido infectadas por el virus. De ahí la importancia de mecanismos indirectos en la neuropatogenia de HIV, ya que las citocinas/quimiocinas pro-inflamatorias liberadas por macrófagos/microglia infectados, la excitoxidad y el stress oxidativo se evidencian como principales causas de injuria neuronal, además de la directamente provocada por proteínas virales. Un mejor conocimiento de la interacción de HIV con su huésped humano está posibilitando el desarrollo de abordajes diganósticos más confiables y de estrategias terapéuticas más efectivas a nivel de SNC

HIV-1 associated neurocognitive disorders (HAND) result from brain infection. They are categorized as dementia, mild cases and asymptomatic cases. The introduction of HAART has markedly decreased dementia but no influence has been observed in mild and asymptomatic cases, since they are still identified in around 50 % of treated patients. Such cognitive dysfunction is the outcome of the loss of neurons which, however, have not been infected by the virus. hence, the importance of indirect mechanisms in HIV neuropathogenesis in which cytokines/chemokines released by infected macrophages/microglia, excitotoxic neuronal injury and oxidative stress are relevant causes of neurodegeneration besides that exerted by viral proteins. A better understanding of the HIV interaction with th human host is enabling the development of more reliable diagnostic biomarkers and more effective therapeutic strategies at CNS level

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and differentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their differentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the differentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell differentiation. We believe that a complete understanding of all molecular players, including vitamin C, in stem cell differentiation will positively impact on the use of stem cell transplantation for neurodegenerative diseases.

Role of PPAR, a Nuclear Hormone Receptor in Neuroprotection.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPAR-alpha is involved in wound healing, stimulation of lipid and folic acid catabolism, inflammation control, inhibition of ureagenesis and peroxisome proliferation. The PPAR/ is involved wound healing, cell proliferation, embryo implantation, adipocyte differentiation, myelination alteration and apoptosis. The PPAR is involved in fat, lipid and calorie utilization, sugar control, inflammation control and macrophage (MQ) matutation. Homocysteine (Hcy) binds to nuclear peroxisome proliferator activated receptor. Increase in PPAR expression decreases the level of nitrotyrosine and increases endothelial nitric oxide concentration, decreases metalloproteinase activity and expression as well as elastinolysis and reverses Hcy-mediated vascular dysfunction. The PPAR initially recognized as a regulator of adipocyte development has become a potential therapeutic target for the treatment of diverse disorders. In addition, the activation of PPAR receptor ameliorates neurodegenerative disease. This review focuses on the recent knowledge of PPAR in neuroprotection and deals with the mechanism of neuroprotection of central nervous system disorder by PPAR.

Trasplante de células troncales: mecanismos de acción para sus usos potenciales en neurología / Stem cells transplant: potentially useful mechanism for neurology

Stem cells have a great potential for the treatment of presently incurable neurological diseases, including spinal trauma, cerebrovascular pathology, brain tumor and neurodegenerative processes, such as Parkinson and Alzheimer's disease, Huntington, multiple sclerosis and amyotrophic lateral sclerosis. Aims: To discuss the characteristics of the various stem cells types having been proposed for cell therapy, and the biological mechanisms responsible for their therapeutic effects. Report: Stem cells can be induced to differentiate into specialized cells such as neurons and glial cells, and they can influence the environment around them, both through the secretion of neurotrophic factors and immunomodulation of the host neuroimmune response. Furthermore, the understanding of the modulatory effect of stem cells could lead to the development of new therapeutic paradigms. Nevertheless, two important limitations of the field are that the ideal source for stem cells is not well defined yet and the mechanism of stem cell mediated functional improvement is not well understood. Conclusions: Research is currently focused on the biological mechanisms of stem cells therapy and the assessment of stem cell programming and delivery to the target regions. Furthermore, future research will increasingly target ways to enhance effectiveness of the stem cell therapy, including its combination with gene therapy. Regardless its enormous potentials, there are still many problems to be solved before clinical application of stem cell therapy can de used in neurological disease patients.

Introducción: Las células troncales tienen un gran potencial para el tratamiento de enfermedades neurológicas actualmente incurables, incluyendo el trauma espinal, patología cerebrovascular y procesos neurodegenerativos como el Parkinson, Alzheimer, Huntington, esclerosis múltiple o la esclerosis lateral amiotrófica. Objetivo: Discutir las características de diversas células troncales que han sido propuestas para terapia celular, y los mecanismos biológicos responsables de sus efectos terapéuticos. Desarrollo: Las células troncales pueden ser inducidas a diferenciarse en células especializadas como neuronas y células gliales, y pueden influenciar su entorno, tanto a través de la secreción de factores neurotróficos como por la inmunomodulación de la respuesta neuroinmune. La comprensión del efecto modulador de las células troncales podría orientar el desarrollo de nuevos paradigmas terapéuticos. Sin embargo, dos limitaciones importantes que persisten son, que la célula troncal ideal aún no está bien definida, y que los mecanismos que median la mejoría inducida por ellas no se comprende bien. Conclusiones: La investigación se enfoca actualmente en los mecanismos biológicos de la actividad terapéutica de las células troncales, en la evaluación de la programación celular y en su acceso a las regiones blanco. La investigación futura se dirigirá progresivamente a encontrar formas de aumentar la efectividad de las células troncales, incluyendo su combinación con terapia genética. Sin embargo, aún existen numerosos problemas que resolver antes que la terapia con células troncales pueda ser usada en pacientes con enfermedades neurológicas.

[Dopamine-synthesizing neurons: an overview of their development and application for cell therapy]

Cell-gene therapy is a dynamic constituent of novel medical biotechnology. Neurodegenerative disorders in which damage to or demise of specific brain cell types plays central role, are clear examples of disease candidate for cell replacement therapy. Dopaminergic [DAergic] neurons biosynthesize dopamine, a vital neurotransmitter in the central nervous system. Due to the involvement of dopamine in a number of critical physiological functions in human and other mammals, disturbed dopamine neurotransmission resulting from DAergic neuron death or damage causes a few known disorders most prominently Parkinson's disease [PD]. DAergic cell replacement therapies proposed as promising approaches for PD treatment have prompted scientists to thoroughly investigate the embryonic development of DAergic neurons and their function in ordinary life. This review summarizes past and current findings in DAergic neuron development and survival. It also briefly looks at the future prospect of DAergic neuron generation in vitro aiming at clinical applications in vivo

possibility of differentiation of human endometrial stem cells into neural cells

In the last few decades, the idea of being able to repair the brain by introducing new cells to repair the damaged areas has become an accepted potential treatment for neurodegenerative diseases. The stromal cell fraction of many tissues and organs has shown in vitro neurogenic differentiation; however, these cell types are limited by availability, invasiveness of extraction and in some cases limited proliferative capacity. Human endometrial adult stem cells have many clinical advantages over the other stem cells. Here, we propose the hypothesis that endometrial adult stem cells may be induced into neural cells

Epigenetics - Gene silencing.

The discovery of the mechanism of RNA interference by ds RNA by Prof. Andrew Fire and Prof. Craig Mello in 1998, gave them the Nobel Prize in 2006. This discovery revealed a new mechanism for gene regulation through “gene silencing” at the transcriptional level (TGS) or at the post-transcriptional level (PTGS), which play a key role in many essential cellular processes. Today dsRNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The immense impact of the discovery of RNA interference (RNAi) on biomedical research and its novel medical applications in the future are reviewed in this article, with particular stress on therapeutic applications of radio-labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of various cancers and neurodegenerative diseases by “gene silencing”. Antisense oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all human genes undergo. The most effective targeting strategy employs simultaneous blocking SnRNP binding sites and splice junctions. Correction of splicing by ASONs can be used to silence mutations causing aberrant splicing as in thalassemia, Duchenne muscular dystrophy and cystic fibrosis. ©

Toxic or tonic, unexploited and emerging potential of Nerium species

Nerium oleander and other Nerium species - Nerium indicum and Nerium odorum popularly known for their toxic effects have been recently shown to be beneficial in ailments other than congestive heart failure for which these were previously utilized. Their neuroprotective action can be exploited to find a possible remedy for neurodegenerative disorders like Alzheimer's disease. The present article deals with the pharmacognostic study, pharmacology and potential of the plant as a future remedy for neuro-degradation

Tratamento farmacológico da doença de Alzheimer / Pharmacological treatment of Alzheimer's disease

O presente artigo de revisão aborda as perspectivas atuais e futuras no tratamento farmacológico da doença de Alzheimer. Os benefícios e limitações da terapia de reposição colinérgica, representada fundamentalmente pelos inibidores das colinesterases, são apresentados com base em dados de pesquisas neurobiológicas, farmacológicas e clínicas, ilustrados pelos principais estudos controlados por placebo e por estudos recentes de metanálise. O papel da memantina nos casos de demência moderada a grave, bem como as perspectivas de seu emprego em associação com os inibidores das colinesterases, são discutidos adicionalmente com base em achados clínicos e neurobiológicos. Discute-se o papel da reposição estrogênica, dos antioxidantes, das estatinas e dos antiinflamatórios no tratamento e na prevenção da demência, levando em consideração os resultados negativos oriundos de estudos clínico-epidemiológicos recentes. Finalmente, são apresentadas algumas perspectivas futuras do tratamento da doença de Alzheimer: entre as estratégias farmacológicas, que têm como objetivo modificar mecanismos patogênicos, são abordadas as diferentes modalidades da terapêutica antiamilóide, com destaque na imunoterapia da doença de Alzheimer.

Cntf: una citokina con potenciales efectos terapéuticos en patologías neurodegenerativas / Cntf: a cytokine with therapeutic potential for the treatment of neurodegenerative diseases

El factor neurotrófico ciliar (CNTF) es una citokina que tiene efectos tróficos sobre neuronas sensitivas y motoras, ya que modifica su expresión génica y afecta su supervivencia. Este trabajo es una revisión de los antecedentes de los efectos de la aplicación de CNTF en modelos animales de neuropatías degenerativas humanas,que han sugerido que esta citokina tiene potencialidades para convertirse en una herramienta para el tratamiento de pacientes con enfermedad de Huntington. También se describen los efectos de la aplicación experimental de CNTF a pacientes con esclerosis lateral amiotrófica. Entre las técnicas empleadas para aplicar CNTF en modelos animales se encuentran la implantación local de células modificadas genéticamente para secretar CNTF y el uso de vectores para insertar genes en neuronas. Estas técnicas de la biología molecular podrían emplearse como herramientas para el tratamiento preventivo de pacientes susceptibles de desarrollar una patología neurodegenerativa o para recuperar las funciones motoras y cognitivas en pacientes que hayan desarrollado la enfermedad.

O uso do litio em idosos: evidencias de sua acao neuroprotetora / The use of lithium by elderly people: evidences of its neuroprotection

O litio esta envolvido em processo de potencial relevancia para a fisiopatologia da doenca de Alzheimer. Existem diversas evidencias de suas acoes neurotroficas e neuroprotetoras em pacientes bipolares. Em parte isso se da...