Noncoding RNAs in Alzheimer's disease DOI Open Access
Maria Laura Idda,

Rachel Munk,

Kotb Abdelmohsen

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2018, Volume and Issue: 9(2)

Published: Jan. 12, 2018

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among elderly worldwide. Despite intense efforts to develop drugs for preventing treating AD, no effective therapies are available as yet, posing growing burden at personal, medical, socioeconomic levels. AD characterized by production aggregation amyloid β (Aβ) peptides derived from precursor protein (APP), presence hyperphosphorylated microtubule-associated Tau (MAPT), chronic inflammation leading neuronal loss. Aβ accumulation responsible histopathological features plaques, neurofibrillary tangles (NFTs), respectively. However, full spectrum molecular factors that contribute pathogenesis not known. Noncoding (nc)RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular (circRNAs), regulate gene expression transcriptional posttranscriptional levels in various diseases, serving biomarkers potential therapeutic targets. There rising recognition ncRNAs have been implicated both onset AD. Here, we review posttranscriptionally pathways discuss interest targeting regulatory therapeutically combat pathology. WIREs RNA 2018, 9:e1463. doi: 10.1002/wrna.1463 This article categorized under: Disease Development > Disease.

Language: Английский

Alzheimer's disease DOI
Philip Scheltens, Bart De Strooper, Miia Kivipelto

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10284), P. 1577 - 1590

Published: March 2, 2021

Language: Английский

Citations

3009
Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression DOI Creative Commons
Xinyi Wang, Guangqiang Sun, Teng Feng

et al.

Cell Research, Journal Year: 2019, Volume and Issue: 29(10), P. 787 - 803

Published: Sept. 6, 2019

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet role of microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link neuroinflammation progression. Using mouse models, discovered that, during alteration composition leads to peripheral accumulation phenylalanine isoleucine, which stimulates differentiation proliferation pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated Th1 immune cells are associated with M1 microglia activation, contributing AD-associated neuroinflammation. Importantly, elevation isoleucine concentrations increase cell frequency blood were also observed two small independent cohorts patients mild cognitive impairment (MCI) due AD. Furthermore, GV-971, sodium oligomannate that demonstrated solid consistent cognition improvement phase 3 clinical trial China, suppresses phenylalanine/isoleucine accumulation, harnesses reverses impairment. Together, our findings highlight dysbiosis-promoted progression suggest novel strategy for therapy by remodelling microbiota.

Language: Английский

Citations

916
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade DOI Creative Commons
Erika N. Cline, Maíra A. Bicca, Kirsten L. Viola

et al.

Journal of Alzheimer s Disease, Journal Year: 2018, Volume and Issue: 64(s1), P. S567 - S610

Published: June 12, 2018

The amyloid-␤ oligomer (A␤O) hypothesis was introduced in 1998.It proposed that the brain damage leading to Alzheimer's disease (AD) instigated by soluble, ligand-like A␤Os.This based on discovery fibril-free synthetic preparations of A␤Os were potent CNS neurotoxins rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998).The mechanism attributed disrupted signaling involving tyrosine-protein kinase Fyn, mediated an unknown toxin receptor.Over 4,000 articles concerning have been published since then, including more than 400 reviews.A␤Os shown accumulate AD-dependent manner human and animal model tissue experimentally, impair learning memory instigate major facets AD neuropathology, tau pathology, synapse deterioration loss, inflammation, oxidative damage.As reviewed Hayden Teplow 2013, A␤O "has all but supplanted amyloid cascade."Despite emerging understanding role played pathogenesis, not yet received clinical attention given plaques, which at core attempts therapeutics diagnostics are no longer regarded as most pathogenic form A␤.However, if momentum research continues, particularly efforts elucidate key aspects structure, a clear path successful modifying therapy can be envisioned.Ensuring lessons learned from recent, late-stage failures applied appropriately throughout therapeutic development will further enable likelihood near-term.

Language: Английский

Citations

700
The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques DOI Creative Commons
Carlo Sala Frigerio, Leen Wolfs, Nicola Fattorelli

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 27(4), P. 1293 - 1306.e6

Published: April 1, 2019

Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus male female App

Language: Английский

Citations

681
The role of adult hippocampal neurogenesis in brain health and disease DOI
Tomohisa Toda, Sarah Parylak, Sara B. Linker

et al.

Molecular Psychiatry, Journal Year: 2018, Volume and Issue: 24(1), P. 67 - 87

Published: April 20, 2018

Language: Английский

Citations

563
Animal models of neurodegenerative diseases DOI
Ted M. Dawson, Todd E. Golde, Clotilde Lagier‐Tourenne

et al.

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(10), P. 1370 - 1379

Published: Sept. 19, 2018

Language: Английский

Citations

486
Amyloid-β-independent regulators of tau pathology in Alzheimer disease DOI
Rik van der Kant, Lawrence S.B. Goldstein, Rik Ossenkoppele

et al.

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 21(1), P. 21 - 35

Published: Nov. 28, 2019

Language: Английский

Citations

447
Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression DOI Creative Commons
Bing Bai, Xusheng Wang, Yuxin Li

et al.

Neuron, Journal Year: 2020, Volume and Issue: 105(6), P. 975 - 991.e7

Published: Jan. 8, 2020

Language: Английский

Citations

435
ApoE4: an emerging therapeutic target for Alzheimer’s disease DOI Creative Commons

Mirna Safieh,

Amos D. Korczyn, Daniel M. Michaelson

et al.

BMC Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: March 20, 2019

The growing body of evidence indicating the heterogeneity Alzheimer's disease (AD), coupled with disappointing clinical studies directed at a fit-for-all therapy, suggest that development single magic cure suitable for all cases may not be possible. This calls shift in paradigm where targeted treatment is developed specific AD subpopulations share distinct genetic or pathological properties. Apolipoprotein E4 (apoE4), most prevalent risk factor AD, expressed more than half patients and thus an important possible therapeutic target. review focuses initially on effects apoE4 as well corresponding cellular animal models suggested molecular mechanisms which mediate them. second part recent apoE4-targeted (from APOE gene to apoE protein its interactors) approaches have been are ready translated human. Further, issue whether due loss protective function gain toxic discussed herein. It both coexist, certain constituents molecule and/or downstream signaling mediating effect, while others associated function. ApoE4 promising target remains understudied. Recent now paving way effective apoE4-directed approaches.

Language: Английский

Citations

380
Practical considerations for choosing a mouse model of Alzheimer’s disease DOI Creative Commons
Joanna L. Jankowsky, Hui Zheng

Molecular Neurodegeneration, Journal Year: 2017, Volume and Issue: 12(1)

Published: Dec. 1, 2017

Alzheimer's disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized the triad of β-amyloid plaques, neurofibrillary tangles, neurodegeneration. Genetic mutations risk factors have been that are either causal or modify progression. These genetic pathological features serve as basis for creation validation mouse models AD. Efforts made in past quarter-century produced over 100 genetically engineered lines recapitulate some aspects AD clinicopathology. valuable resources understanding interactions contribute to cellular reactions engaged response. Here we focus on widely used stalwarts field recently developed bellwethers future. Rather than providing a summary each model, endeavor compare contrast approaches employed discuss their respective advantages limitations. We offer critical account variables which may inconsistent findings should be considered when choosing model interpreting results. hope present an insightful review current provide practical guide selecting best matched experimental question at hand.

Language: Английский

Citations

377