Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes

AbstractAntiretroviral therapeutics (ART) have effectively increased the long-term survival of HIV-1 infected individuals. However, the prevalence of HIV-1 associated neurocognitive disorders (HAND) has increased and so too have clinical manifestations and pathological features of Alzheimer ’s disease (AD) in people living with HIV-1/AIDS. Although underlying mechanisms are not clear, chronic exposure to ART drugs has been implicated in the development of AD-like symptoms and pathology. ART drugs are categorized according to their mechanism of action in controlling HIV-1 levels. All ART drugs are organic compounds that can be classified as being either weak acids or weak bases, and these physicochemical properties may be of central importance to ART drug-induced AD-like pathology because weak bases accumulate in endolysosomes, weak bases can de-acidify endolysosomes where amylo idogenesis occurs, and endolysosome de-acidification increases amyloid beta (Aβ) protein production and decreases Aβ degradation. Here, we investigated the effects of ART drugs on endolysosome pH and Aβ levels in rat primary cultured neurons. ART drugs that de-acidified endolysosomes increased Aβ levels, whereas those that acidified endolysosomes decreased Aβ levels. Acidification of endolysosomes with the mucolipin transient receptor potential (TRPML) channel agonist ML-SA1 blocked ART drug-induced increases in Aβ levels. Further, ART drug-induced endolysosome de-ac...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research

Related Links:

Myelin is the sheathing of nerves, essential to their function. Excessive loss produces disabling and ultimately fatal conditions such as multiple sclerosis, but we all lose myelin integrity to some degree as a consequence of the damage and dysfunction of degenerative aging. This most likely contributes to cognitive decline and other age-related issues. A number of different approaches have been identified to boost the operation of the normal maintainance processes that remyelinate nerves, such as FGF21 upregulation, or increasing the size of remyelinating cell populations. Here, researchers discover another possible trigg...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Ronald S. Brookmeyer, professor of biostatistics and expert on how statistical tools can help address global public health challenges, will become the dean of the UCLA Fielding School of Public Health, effective Jan. 15.A member of the UCLA faculty since 2010, Brookmeyer has served as interim dean of the Fielding School since November 2018.“I am humbled by this opportunity to advance public health at our extraordinary public university,” Brookmeyer said. “With Fielding School faculty, staff and students, as well as colleagues and communities in our hometown of Los Angeles and far beyond, I look forward to...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Authors: Arjmand B, Larijani B, Sheikh Hosseini M, Payab M, Gilany K, Goodarzi P, Parhizkar Roudsari P, Amanollahi Baharvand M, Hoseini Mohammadi NS Abstract Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. The emergence of recombinant DNA technology which provides the possibility of fetal genetic s...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
(Alzheimer's Association) More than ever before, Alzheimer's researchers understand that a variety of approaches will be needed - most likely used in combination - for effective treatment of the disease.
Source: EurekAlert! - Social and Behavioral Science - Category: International Medicine & Public Health Source Type: news
ou Kaufer Viruses of the genus Roseolovirus belong to the subfamily Betaherpesvirinae, family Herpesviridae. Roseoloviruses have been studied in humans, mice and pigs, but they are likely also present in other species. This is the first comparative analysis of roseoloviruses in humans and animals. The human roseoloviruses human herpesvirus 6A (HHV-6A), 6B (HHV-6B), and 7 (HHV-7) are relatively well characterized. In contrast, little is known about the murine roseolovirus (MRV), also known as murine thymic virus (MTV) or murine thymic lymphotrophic virus (MTLV), and the porcine roseolovirus (PRV), initially incorrect...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
CONCLUSIONS: Use of HAs is associated with delayed diagnosis of AD, dementia, depression, anxiety, and injurious falls among older adults with HL. Although we have shown an association between use of HAs and reduced risk of physical and mental decline, randomized trials are needed to determine whether, and to what extent, the relationship is causal. The Study in Context: Hearing aids, by reducing cognitive load, can improve brain function in persons with hearing loss 46.7 million Americans have Alzheimer’s Disease brain pathology today, so it’s urgent to prevent or at least delay progression to clinical disea...
Source: SharpBrains - Category: Neuroscience Authors: Tags: Cognitive Neuroscience Health & Wellness Technology anxiety dementia depression fall-related injuries hearing aid hearing loss Medicare older-adults Source Type: blogs
A novel PET imaging technique has uncovered high levels of ischemia in patients...Read more on AuntMinnie.comRelated Reading: PET/MRI sheds light on cerebral vascular risk factors Flortaucipir-PET shows tau accumulation after one TBI PET, MRI show physical activity aids brain health Carbon-11 PET detects brain inflammation after Lyme disease SNMMI: Cerebrovascular risk tied to Alzheimer's disease
Source: Headlines - Category: Radiology Source Type: news
PET/MRI scans show middle-aged adults with high vascular risk factors have...Read more on AuntMinnie.comRelated Reading: PET, MRI show physical activity aids brain health SNMMI: Cerebrovascular risk tied to Alzheimer's disease MRI ties high blood pressure to dementia risk PET links amyloid, vascular factors to cognitive decline PET links midlife vascular risk factors to more amyloid
Source: Headlines - Category: Radiology Source Type: news
DISCUSSION: In the future, managers and employees in acute care hospitals will be able to find a wide range of suggestions in comprehensive guidelines from the iso-Institute on the modular implementation of dementia-sensitive hospitals, which is backed up by tried and tested and effective aids to action, instruments, process descriptions, etc. The guidelines will also be available in the form of a comprehensive list of recommendations. PMID: 31628614 [PubMed - as supplied by publisher]
Source: Zeitschrift fur Gerontologie und Geriatrie - Category: Geriatrics Authors: Tags: Z Gerontol Geriatr Source Type: research
Brain maps based on functional MRI (fMRI) scans are proving useful in predicting...Read more on AuntMinnie.comRelated Reading: Can MRI of healthy brains explain head trauma damage? Advanced MRI technique confirms dementia risk PET, MRI show physical activity aids brain health MRI links brain region to dementia, auditory deterioration DTI-MRI offers window into Alzheimer's risk
Source: Headlines - Category: Radiology Source Type: news
More News: Alzheimer's | Brain | Drugs & Pharmacology | HIV AIDS | Neurology | Organic | Pathology