Protective effect of brain-derived neurotrophic factor on retinal neurovascular unit / 国际眼科杂志(Guoji Yanke Zazhi)

Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.

Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

Role of Aluminium in Alzheimer’s disease: Ultrastructural Study in Rat Hippocampus

Background: Exposure to high levels of aluminium (Al) leads to neurotoxicity. Hippocampus is one of the preferred sites of aluminium accumulation. Nevertheless, the role of Al in Alzheimer’s disease (AD) remains controversial and there is little proof directly interlinking Al to AD. Aims: The present study was undertaken to find out the occurrence of AD pathogenesis in Hippocampus under moderate aluminium exposure in rats. Materials and Methods: Adult rats were divided into control (C) and aluminium treated (E) groups having eight animal each. The rats in group E were exposed to aluminium 4.2 mg/kg body weight for three months with due approval from Institute Animal Ethics Committee. The hippocampus was processed for histopathological and electron microscopy observation. Results: Moderate Al intake produces significant reduction in the count of Pyramidal cells in hippocampus identified by shrunken cells as well as pyknosis in cell bodies. The differences between the cell numbers in all groups were found to be statistically significant (P < 0.05). Cornu Ammonis (CA) exhibited significantly reduced nissl bodies with a marked reduction in neuronal cell loss. Neurofibrillary tangle and plaques were not seen in the given dose of Al exposure. Electron microscopy from experimental group showed that the majority of neurons were disintegrating, the nuclear membrane has ruptured, and nucleoli appeared significantly distorted. The chromatin condensed and the mitochondria had disintegrated. Many vacuoles and lipofuscin sediment in cytoplasm, as compared to the control group noted. Conclusion: Present data demonstrated that moderate chronic aluminium exposure 4.2mg/kg body weight induced neurodegeneration in hippocampus but not significant for Alzheimer’s disease pathogenesis.

The Ameliorative Effect of Ashwagandha- Withania somnifera (L.) Dunal on park25 Induced Neurodegeneration in Drosophila melanogaster Parkinson’s Disease Model

Ashwagandha - Withania somnifera (L.) Dunal is a perennial shrub belonging to the family Solanaceae. Ashwagandha has been used for over 3000 years in traditional Indian Ayurveda for treatment of various neurological, and stress disorders. The root of Ashwagandha (ASH) is regarded as a tonic, aphrodisiac, narcotic, diuretic, anthelmintic, astringent, thermogenic and stimulant. Ashwagandha with other herbal decoctions was recognized to treat Kampavatha (Parkinson’s Disease) since 18th century. With this wide array of ethnopharmacological relevance, Ashwagandha has been recognized as one of the prominent complementary and alternative medicine to treat many neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s disease (PD). There is a prominent increase in the cases of AD and PD all over the world and it demands the requirement of complementary and alternative herbal remedies with no/minimal side effects. Many genetic factors are responsible for the onset and progression of PD. Loss-of-function mutations in the parkin gene are a major cause of early onset of autosomal recessive juvenile parkinsonism (AR-JP). Drosophila park25 loss of function mutants exhibit significantly increased number of mitochondria-endoplasmic reticulum contacts and a significantly decreased number of dopaminergic neurons in the adult brain which is the main cause of PD condition. Several studies have demonstrated the ability of Ashwagandha in imparting neuroprotection, improved locomotory ability, memory and learning abilities. The challenge lies in scrutinizing the mechanism and the pathways involved in the neuroprotective properties of this well-known herb. Here in our study, we test the possible neuroprotective effect of Ashwagandha on park25 mutants of Drosophila using lifespan analysis and climbing disability as a disease marker. Parkinson’s mimicking flies were administered with aqueous extraction of Ashwagandha-root mixed with the fly food and subjected to negative geotaxis assay. We observed that there is a prominent increase in the climbing ability in park25 treated flies compared to its age-matched untreated flies. This is the first report showing that, aqueous extraction of Ashwagandha-root extract was able to ameliorate the disease phenotype in the park25 Drosophila Parkinson’s disease model.

Research progress in the intervention of Chinese herb monomers on diabetic retinal neurodegeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)has been traditionally considered a purely microvascular disease in the retina. Currently, mainstream therapies focus only on advanced vascular complications and a single molecular target-vascular endothelial growth factor(VEGF). However, the research is shifting towards a more comprehensive view that DR is a neurovascular disease caused by neurovascular unit(NVU)injury. In the early stage of DR, diabetic retinal neurodegeneration(DRN)dominates and may precede the retinal microvascular abnormalities. Moreover, neuronal apoptosis can further lead to microvascular injury and blood-retinal barrier(BRB)disruption. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse DRN. However, no drug targeting DRN has been approved for clinical use. In recent years, it has become a trend to study the protective effect of traditional Chinese medicine on the retina. The primary research focuses on Chinese herb monomers. This article reviews the research status of representative monomers in DRN to provide references for the early treatment of DR and development of new drugs.

A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.

Aluminum toxicity induced Alzheimer's Disease and its potential treatment using antioxidants - a review

Abstract Over the years, a handful of drugs have been approved to be used in the fight against Alzheimer's Disease but unfortunately none of these drugs have proven to be solid-treatments. Alzheimer's Disease is one of the most prominent diseases observed in the elderly population. In this review article, we discuss how aluminum toxicity can lead to neuro degeneration. Aluminum is abundantly present on the earth's crust and hence becomes easily accessible to man. This makes it an obvious choice in the preparation of numerous substances, packaging, etc. Such wide usage of the metal can pave an easy access to the body, leading to toxicities. Aluminum toxicity has been linked to oxidative stress which has an established relation with neurodegeneration and mitochondrial damage. We also discuss how consumption of antioxidants can be useful in combating oxidative stress.

Traditional Chinese Medicine Monomers in Treatment of Diabetic Retinopathy by Regulating PI3K/Akt Signaling Pathway： A Review / 中国实验方剂学杂志

Diabetes retinopathy （DR） is an important cause that threatens the visual health of adults. There are some treatment methods of western medicine with definite efficacy， such as anti-vascular endothelial growth factor and laser photocoagulation， but they have many adverse reactions such as intraocular infection and visual field damage. Traditional Chinese medicine （TCM） therapies are safe and effective， which can complement western medicine. Phosphatidylinositol3-kinase （PI3K）/protein kinase B （Akt） signaling pathway regulates a range of processes including glucose metabolism， cell proliferation， and cell transcription and apoptosis， which is closely related to the occurrence and development of DR. Numerous studies have shown that TCM monomers can participate in maintaining the integrity of blood-retinal barrier and inhibiting retinal neovascularization and neurodegeneration in many aspects such as inhibiting oxidative stress and alleviating inflammatory reaction by regulating the PI3K/Akt pathway， so as to delay the progress of DR. Therefore， this study reviewed PI3K/Akt pathway and its relationship with DR， as well as the TCM monomers in interfering with DR based on PI3K/Akt pathway to provide some ideas for the prevention and treatment of DR in integrated TCM and western medicine.

Elevated phosphorylated ubiquitin level elicits neuro-degeneration by aggregating the decline of ubiquitin-dependent proteasomal degradation / 中国药理学与毒理学杂志

OBJECTIVE To determine the roles of phosphorylated ubiquitin(pUb)on ubiquitin-dependent proteasomal(UPS)degradation activity,and the roles of pUb on neurodegeneration.METHODS We use PTEN induced kinase 1(PINK1)to phosphorylate ubiquitin.The Ub/S65A cannot be phosphorylated by PINK1,and was used to antagonize the roles of pUb.The Ub/S65E was used to mimic the roles of pUb.The roles of pUb on UPS degradation activity were determined by immunoflu-orescence,Western blot and TIRF microscope at cellular and protein level.The roles of pUb on neurodegeneration were determined by behavior tests,immunofluorescence,Golgi staining,TEM,Western blot and proteomics sacle in mouse.RESULTS The level of soluble PINK1(sPINK1)and pUb increased in the neurons of aged mouse brain,and in the cells upon the administration of MG132,a proteasome inhibitor.The elevation of sPINK1 and pUb was accompanied by protein aggregation upon aging or the proteasomal inhibition.The pink1 knockout alleviated proteasomal inhibition induced protein aggregation and association of ubiquitinated proteins with proteasome.The over-expression of sPINK1 increased pUb level in hippocampal neuron,which chronically induced protein aggregation,mitochondrial damage and damage the structure of neuronal spines.Such neuronal injury lead to cognitive impairment of mice.The roles of sPINK1 was reversed by co-expression with Ub/S65A,and was mimic by over-expression with Ub/S65E.CONCLUSION The phosphorylation of ubiquitin aggravates UPS degrada-tion,and accelerates neuronal degeneration upon the decline of proteasomal degradation in aging and age-related neuronal diseases.

Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis / 神经科学通报·英文版

Multiple sclerosis (MS) is regarded as a chronic inflammatory disease that leads to demyelination and eventually to neurodegeneration. Activation of innate immune cells and other inflammatory cells in the brain and spinal cord of people with MS has been well described. However, with the innovation of technology in glial cell research, we have a deep understanding of the mechanisms of glial cells connecting inflammation and neurodegeneration in MS. In this review, we focus on the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the pathogenesis of MS. We mainly focus on the connection between glial cells and immune cells in the process of axonal damage and demyelinating neuron loss.

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.

Hierro: desde la homeostasis a la muerte por ferroptosis / Iron: from normal homeostasis to death by ferroptosis

Resumen El hierro (Fe) es un elemento vital para casi todos los organismos debido a su facilidad para donar y aceptar electrones. Es cofactor de muchas proteínas y enzimas necesarias para la adecuada utilización del oxígeno y la generación de energía. Su desregulación se relaciona a procesos de estrés oxidativo y muerte celular mediada por Fe(II) denominada ferroptosis. Las células de mamíferos utilizan múltiples mecanismos para garantizar la adquisición del hierro como nutriente esencial, que se encuentra oxidado [Fe(III)], y que debe ser reducido a Fe(II) para su adecuada utilización intracelular. Cada etapa de transferencia del hierro a través de las membranas biológicas exige una reconversión de su estado de oxidado a reducido y viceversa, dependiendo del paso metabólico implicado. La distorsión de dichos procesos se asocia con varias enfermedades: desde la deficiencia de hierro debida a defectos en la adquisición o distribución del metal, que causa anemia, a la sobrecarga de hierro que resulta de una absorción excesiva de hierro o en una utilización defectuosa, que causa una sobreoferta de Fe(II) en los tejidos y que lleva a un daño oxidativo y a la muerte celular. Existen múltiples mecanismos regulatorios que en conjunto aseguran el equilibrio en la homeostasis del hierro. Esta actualización describe los avances recientes en las vías reguladoras del hierro, así como en los mecanismos subyacentes al tráfico de dicho elemento desde su absorción, principalmente biodistribución y su uso intracelular, quizás el área más importante donde se define su adecuada utilización o la muerte celular por ferroptosis.

Abstract Iron (Fe) is a vital element for almost all organisms due to its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for the proper use of oxygen and energy generation, and its deregulation is related to the processes of oxidative stress and iron-mediated cell death called ferroptosis. Mammalian cells use multiple mechanisms to ensure the acquisition of iron as an essential nutrient, which is normally oxidised in the form of Fe(III) and must be reduced to Fe(II) for adequate intracellular use. Each stage of iron transfer across biological membranes requires a reconversion of its state from oxidised to reduced and vice versa, depending on the metabolic step involved. Distortion of these processes is associated with various diseases, such as iron deficiency due to defects in the acquisition or distribution of the metal that causes anemia, as well as iron overload from excessive iron absorption or defective use, which results in an oversupply of Fe(II) in tissues leading to oxidative damage and cell death. There are multiple regulatory mechanisms that together ensure the balance in iron homeostasis. This update describes the recent advances in the iron regulatory pathways, as well as in the mechanisms underlying iron trafficking from its absorption, mainly biodistribution and its intracellular use, perhaps the most important area where its adequate utilisation or cell death by ferroptosis is defined.

Resumo O ferro (Fe) é um elemento vital para quase todos os organismos devido à sua capacidade de doar e aceitar elétrons com relativa facilidade. O ferro serve como cofator para muitas proteínas e enzimas necessárias para o uso adequado do oxigênio e geração de energia, e a sua desregulação está relacionada a processos de estresse oxidativo e morte celular mediada por Fe(II) denominado ferroptose. As células de mamíferos utilizam múltiplos mecanismos para garantir a aquisição de ferro como nutriente essencial, que normalmente é oxidado na forma de Fe(III) e deve ser reduzido a Fe(II) para o uso intracelular adequado. Cada estágio de transferência de Fe através das membranas biológicas requer uma reconversão de seu estado de oxidado para reduzido e vice-versa, dependendo da etapa metabólica envolvida. A distorção desses processos está associada a várias doenças: desde a deficiência de ferro devido a defeitos na aquisição ou distribuição do metal que causa a anemia, até a sobrecarga de ferro resultante da absorção excessiva de ferro ou utilização defeituosa, que causa um excesso de oferta de Fe(II) nos tecidos levando ao dano oxidativo e morte celular. Existem múltiplos mecanismos regulatórios que juntos garantem o equilíbrio na homeostase do ferro. Esta atualização descreve os avanços recentes nas vias reguladoras do ferro, bem como nos mecanismos subjacentes ao tráfico deste elemento desde a sua absorção, principalmente biodistribuição e seu uso intracelular, talvez a área mais importante onde sua utilização adequada ou morte celular por ferroptose é definido.

Role of Nrf2 Pathway Activation in Neurological Disorder: A Brief Review

Oxidative stress plays a crucial role in the emergence of numerous neurodegenerative diseases, with protein accumulation and mitochondrial damage, which result in neurological disorders. To minimize oxidative stress, several defensive mechanisms protect nerve cells by releasing antioxidants such as nuclear erythroid factor2 (Nrf2)-Kelch-like ECH-associated protein1 (Keap1) signaling pathway activation has been proved to be a prospective treatment to reduce oxidative stress and neuroinflammation for protection of neurons in a variety of neurological disorders. In this review, we focus beneficial role of Nrf2 in Alzheimer’s and Parkinson’s diseases. Nrf2 is proved to be a master regulator of antioxidants by releasing over 250 cytoprotective genes aimed at oxidative stress and neuroinflammation. In animal studies Nrf2 activation is proved to improve autophagy, mitochondrial biogenesis, and Suppression of inflammatory cytokinin which protects neuronal cells and inhibit progressive neurodegeneration.

Clinical Study of Neurodegenerative Treatment on Glaucoma by Insulin Intravitreal Injection

Purpose: Our trail was to study insulin intravitreal injection’s (IIV) efficacity and safety to treat glaucoma neurodegeneration.Methods: Eleven subjects (11eyes) were recruited;10 patients treated in a double masked randomized sham controlled including 5 patients received one IIV injection 3UI and 5 patients received one injection of balanced salt solution(BSS) 3UI. A follow up during 168days was realized using Optical Coherence Tomography(OCT) and visual field(VF).The eleventh patient received two IIV injection without masking the injection content within one month between each injection and followed up for 877days.All the patients have a correct ocular pressure and no ocular treatment was stopped.Results: The 5 patients who received IIV revealed a swift improvement of decibel (DB), and remains stable during the first month. The average improvement was 6.62DB during 168days.The 5 patients treated with one BSS injection showed no significant improvement regaining 1. 45DB.The last patient who received two injections showed increase from 7.54DB to 17.22DB with a functional amelioration of 9. 68DB.The OCT examination showed a structural improvement during the first month, then returned to the initial value. No complication was observed during and after the treatment.Conclusion: Insulin shows not only efficacity and safety but more than that, the visual field(VF) of the patients became stable and show no deterioration in all the follow up, which confirmed that insulin act to improve the function rather than structure. it means insulin reconnect the stoma and improve the neurite outgrowth This treatment will change the evolution of this pathology and protect the glaucomatous patients against blindness.

A Rare Incidence of Accelerated Dementia Onset Post Traumatic Brain Injury in a 22 year old: a case report

A 22 year old male presented with symptoms of fast-escalating cognitive degeneration and behavioral impairment after a period of clinical recovery post severe traumatic brain injury (TBI). Neuroimaging found extensive mild-moderate cortico-cerebral atrophy not really corresponding to his primary TBI lesions. A diagnosis of dementia [ICD F02.8] was made and patient was treated accordingly, in conjunction with Neurology services, with emphasis on neuro-cognitive rehabilitation. Extensive testing could not find any other likely causes for this condition, which was then postulated to be generalized secondary post-TBI neurodegenerative changes. His symptoms are currently improved and stabilized with ongoing maintenance-phase management, but as this condition is not reversible – this case report discusses likely etiopathological processes and corresponding management options (both presently available and those likely to become so in near future) to be aware of.

Nanopolyphenols: Perspective on oxidative stress-induced diseases

Recently nanopolyphenols are gaining widespread interest in the drug discovery domain. Nanonization of polyphenols has greatly affected the therapeutic index owing to improvement in pharmacokinetic and biopharmaceutical obstacles linked with the use of natural polyphenols. They have been looking at an emerging paradigm for an array of disease symptoms. In this article, we have explored the therapeutic potential of nanopolyphenols in oxidative stress-induced diseases such as neurodegeneration, cancer, obesity, and diabetes. This article will present the current state of the art of various nanopolyphenols targeting oxidative stress-induced diseases. The advanced fabrication strategies presented for polyphenols including nanocrystal, mesoporous silica nanoparticles, nanoparticles, nanoliposome, gold nanoparticle, and nanosuspension are discussed. The information presented in light of recent in vitro, in vivo, and clinical evidence for nanoformulation and delivery of polyphenols may show a new dimension to future research in the realm of herbal therapy for oxidative stress- induced diseases. Significant information on the molecular mechanisms underlying linkages of oxidative stress with neurodegenerative diseases, cancer, obesity, and diabetes is discussed. Valuable information on dietary polyphenols in these diseases and their clinical data is presented. Based on different experimental evidence, the review findings support phenomenal therapeutic strategies for nanopolyphenolic fabrication with extended benefits and a condensed time frame. The status of clinical trials conducted on nanopolyphenols is presented. Although clinical trials conducted on nanopolyphenols for mentioned diseases are few, we have tried to present as much available clinical data in this article.

Adapting AVATAR Therapy: Using available digital technology for people living with Auditory Verbal Hallucinations in Low and Middle Income Countries

A 22 year old male presented with symptoms of fast-escalating cognitive degeneration and behavioral impairment after a period of clinical recovery post severe traumatic brain injury (TBI). Neuroimaging found extensive mild-moderate cortico-cerebral atrophy not really corresponding to his primary TBI lesions. A diagnosis of dementia [ICD F02.8] was made and patient was treated accordingly, in conjunction with Neurology services, with emphasis on neuro-cognitive rehabilitation. Extensive testing could not find any other likely causes for this condition, which was then postulated to be generalized secondary post-TBI neurodegenerative changes. His symptoms are currently improved and stabilized with ongoing maintenance-phase management, but as this condition is not reversible – this case report discusses likely etiopathological processes and corresponding management options (both presently available and those likely to become so in near future) to be aware of..

Family Herpesviridae and neuroinfections: current status and research in progress

This article addresses the relationship between human herpesviruses (HHVs) and neuroinfections. Alphaherpesviruses, betaherpesviruses and gammaherpesviruses are neurotropic viruses that establish latency and exhibit reactivation capacity. Encephalitis and meningitis are common in cases of HHV. The condition promoted by HHV infection is a purported trigger for certain neurodegenerative diseases. Ongoing studies have identified an association between HSV-1 and the occurrence of Alzheimer's disease, multiple sclerosis and infections by HHV-6 and Epstein-Barr virus. In this review, we highlight the importance of research investigating the role of herpesviruses in the pathogenesis of diseases that affect the nervous system and describe other studies in progress.

Os impactos da neuroinflamação na doença de Alzheimer / The impacts of neuroinflamation on Alzheimer's disease

A Doença de Alzheimer (DA) consiste em um grande problema de saúde pública no Brasil e no mundo. Trata-se de uma doença neurodegenerativa, em que ocorre perda progressiva de neurônios e atrofia das regiões cerebrais. Essa degeneração está associada principalmente ao depósito de duas proteínas tóxicas: a proteína beta-amiloide e a proteína Tau, uma vez que estas proteínas se encontram acumuladas, elas prejudicam a ocorrência de sinapses nervosas. Apesar de extremamente prevalente na população mais idosa, suas causas ainda não estão bem esclarecidas, sendo que vários fatores já foram apontados como possíveis motivos para o surgimento do depósito destas proteínas, levando assim a neurodegeneração. Recentemente, tem se estudado o papel da inflamação, que é fundamental durante todo o curso da doença, tanto para a eliminação das proteínas tóxicas quanto para a proteção de neurônios. Um funcionamento anormal do processo inflamatório poderia dificultar a eliminação das proteínas e acentuar a perda neuronal. Com isso essa revisão de literatura tem como objetivo descrever os principais fatores imunológico que se encontram alterados na Doença de Alzheimer e como isso pode contribuir para o quadro neurodegenerativo.

Alzheimer's Disease (AD) is a major public health problem in Brazil and worldwide. It is a neurodegenerative disease, in which there is a progressive loss of neurons and atrophy of brain regions. This degeneration is mainly associated with the deposition of two toxic proteins, the beta-amyloid protein and the Tau protein, once these proteins are accumulated, they impair the occurrence of nerve synapses. Despite being extremely prevalent in the older population, its causes are still not well understood, and several factors have already been pointed out as possible reasons for the emergence of the deposit of these proteins, thus leading to neurodegeneration. Recently, the role of inflammation, which is fundamental throughout the course of the disease, has been studied, both for the elimination of toxic proteins and for the protection of neurons. An abnormal functioning of the inflammatory process could hinder the elimination of proteins and accentuate the neuronal loss Thus, this literature review aims to describe the main immunological factors that are altered in Alzheimer's Disease and how this can contribute to the neurodegenerative picture.