Sex and the development of Alzheimer's disease

Journal of Neuroscience Research, Journal Year: 2016, Volume and Issue: 95(1-2), P. 671 - 680

Published: Nov. 7, 2016

Men and women exhibit differences in the development progression of Alzheimer's disease (AD). The factors underlying sex AD are not well understood. This Review emphasizes contributions steroid hormones to relationship between AD. In women, events that decrease lifetime exposure estrogens generally associated with increased risk, whereas estrogen-based hormone therapy administered near time menopause may reduce risk. men, do age-related reduction significantly Rather, normal depletions testosterone plasma brain predict enhanced vulnerability Both androgens exert numerous protective actions adult increase neural functioning resilience as specifically attenuating multiple aspects AD-related neuropathology. Aging diminishes activational effects sex-specific manners, which is hypothesized contribute aging Sex also drive through their organizational during developmental sexual differentiation brain. Specifically, early confer inherent female advanced age. combined steroids yield distinct pathogenesis, a significant variable must be more rigorously considered future research. © 2016 Wiley Periodicals, Inc.

Language: Английский

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The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases

Frontiers in Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: May 16, 2017

TThe accumulation of misfolded proteins in the human brain is one critical features many neurodegenerative diseases, including Alzheimer's disease (AD). Assembles beta-amyloid (Aβ) peptide – either soluble (oligomers - Aβ) or insoluble (plaques) and tau protein, which form neurofibrillary tangles, are major hallmarks AD. Chaperones co-chaperones regulate protein folding client maturation, but they also target aggregated for refolding degradation, mostly by proteasome. They an important line defense against part cellular quality control system. The heat shock (Hsp) family, particularly Hsp70 Hsp90, plays a this process it well known to misfolding variety levels toxicity However, role Hsp90 regulating not yet fully understood. For example, knockdown its C. elegans model Aβ leads increased toxicity. On other hand, use inhibitors AD mouse models reduces toxicity, normalizes synaptic function. Stress-inducible phosphoprotein 1 (STI1), intracellular co-chaperone, mediates transfer clients from Hsp90. Importantly, STI1 has been shown aggregation amyloid-like yeast. In addition function, can be secreted diverse cell types, astrocytes microglia function as neurotrophic ligand triggering signaling via prion (PrPC). Extracellular prevent toxic (i) interfering with binding PrPC (ii) pro-survival cascades. Interestingly, decreased increase amyloid model. review, we will discuss extracellular Hsp70/Hsp90 chaperone network mechanisms underlying particular focus on disease.

Language: Английский

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Il10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology

Neuron, Journal Year: 2015, Volume and Issue: 85(3), P. 534 - 548

Published: Jan. 22, 2015

Language: Английский

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IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Proceedings of the National Academy of Sciences, Journal Year: 2016, Volume and Issue: 113(19)

Published: April 18, 2016

Significance Dysfunction of the innate immune system is involved in pathogenesis Alzheimer’s disease (AD); however, pathophysiological mechanisms underlying these dysfunctions are unclear. Here we report that stimulation IL-33/ST2 signaling rescues memory deficits and reduces accumulation β-amyloid APP/PS1 mice exhibit select pathologies associated with AD. Although impaired early progression AD, IL-33 injection contextual mice. skews microglia toward an alternative activation state enhanced Aβ phagocytic capacity elevated antiinflammatory gene expression, which results a decreased proinflammatory response brain. Thus, this study suggests can be developed as new therapeutic intervention for

Language: Английский

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A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders

Clinical Microbiology Reviews, Journal Year: 2022, Volume and Issue: 35(1)

Published: Jan. 5, 2022

The human body is full of an extensive number commensal microbes, consisting bacteria, viruses, and fungi, collectively termed the microbiome. initial acquisition microbiota occurs from both external maternal environments, vast majority them colonize gastrointestinal tract (GIT). These microbial communities play a central role in maturation development immune system, nervous GIT system are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect composition gut microbiota. Recent publications have highlighted that imbalance microflora, known as dysbiosis, associated with onset progression neurological disorders. Moreover, characterization microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical clinical research on interventions related to microbiome treating conditions, autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's epilepsy, stroke, hold significant promise. This review aims present comprehensive overview potential involvement pathogenesis particular emphasis microbe-based therapies and/or diagnostic biomarkers. discusses health benefits administration probiotics, prebiotics, postbiotics, synbiotics fecal transplantation

Language: Английский

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