Region-specific glial homeostatic signature in prion diseases is replaced by a uniform neuroinflammation signature, common for brain regions and prion strains with different cell tropism.

Region-specific glial homeostatic signature in prion diseases is replaced by a uniform neuroinflammation signature, common for brain regions and prion strains with different cell tropism. Neurobiol Dis. 2020 Jan 27;:104783 Authors: Makarava N, Chang JC, Molesworth K, Baskakov IV Abstract Chronic neuroinflammation is recognized as a major neuropathological hallmark in a broad spectrum of neurodegenerative diseases including Alzheimer's, Parkinson's, Frontal Temporal Dementia, Amyotrophic Lateral Sclerosis, and prion diseases. Both microglia and astrocytes exhibit region-specific homeostatic transcriptional identities, which under chronic neurodegeneration, transform into reactive phenotypes in a region- and disease-specific manner. Little is known about region-specific identity of glia in prion diseases. The current study was designed to determine whether the region-specific homeostatic signature of glia changes with the progression of prion diseases, and whether these changes occur in a region-dependent or universal manner. Also of interest was whether different prion strains give rise to different reactive phenotypes. To answer these questions, we analyzed gene expression in the thalamus, cortex, hypothalamus and hippocampus of mice infected with 22 L and ME7 prion strains using a Nanostring Neuroinflammation panel at the subclinical, early clinical and advanced stages of the disease. We found that at the preclinical stage of the disease, the region-s...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research

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Abstract The deposition of proteins of abnormal conformation is one of the major hallmarks of the common neurodegenerative diseases including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, frontotemporal dementia, and prion diseases. Protein quality control systems have evolved to protect cells and organisms against the harmful consequences of abnormally folded proteins that are constantly produced in small amounts. Mutations in rare inherited forms of neurodegenerative diseases have provided compelling evidence that failure of protein quality control systems can drive neurodegeneration. With extensive k...
Source: Current Opinion in Neurobiology - Category: Neurology Authors: Tags: Curr Opin Neurobiol Source Type: research
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of gr...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as to the injury and death of neurons due to an excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in a dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. De...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
CONCLUSION: Air pollution is associated with increased risk of certain common neurological disorders. More specific studies are needed to investigate the impact of seasonal haze on neurological conditions in Southeast Asia. PMID: 32200394 [PubMed - in process]
Source: Annals of the Academy of Medicine, Singapore - Category: General Medicine Authors: Tags: Ann Acad Med Singapore Source Type: research
Xiao Neurodegenerative diseases (NDs) affect millions of people worldwide. Characterized by the functional loss and death of neurons, NDs lead to symptoms (dementia and seizures) that affect the daily lives of patients. In spite of extensive research into NDs, the number of approved drugs for their treatment remains limited. There is therefore an urgent need to develop new approaches for the prevention and treatment of NDs. Glycans (carbohydrate chains) are ubiquitous, abundant, and structural complex natural biopolymers. Glycans often covalently attach to proteins and lipids to regulate cellular recognition, adhes...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
AbstractOver the last two decades, a number of studies have underlined the importance of lysosomal ‐based degradative pathways in maintaining the homeostasis of post‐mitotic cells, and revealed the remarkable contribution of a functional autophagic machinery in the promotion of longevity. In contrast, defects in the clearance of organelles and aberrant protein aggregates have been linked to a ccelerated neuronal loss and neurological dysfunction. Several neurodegenerative disorders, among which Alzheimer disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) to name a few, are associated wi...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research
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Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
AbstractThe genetic variant rs72824905-G (minor allele) in thePLCG2 gene was previously associated with a reduced Alzheimer ’s disease risk (AD). The role ofPLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
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