Astrocyte Heterogeneity: Impact to Brain Aging and Disease DOI Creative Commons
Isadora Matias,

Juliana Morgado,

Flávia Carvalho Alcântara Gomes

et al.

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: March 19, 2019

Astrocytes, one of the largest glial cell population in Central Nervous System, play key function several events brain development and function, such as synapse formation control neurotransmitters release uptake, production trophic factors neuronal survival. Initially described a homogenous population, evidences have pointed that astrocytes are highly heterogeneous, both morphologically functionally, within same region, across different regions. Recent findings suggest heterogeneity expression profile proteins involved astrocyte may predict selective vulnerability regions to specific diseases, well age-related cognitive decline. However, molecular mechanisms underlying these changes, either aging disease scarce. Neuroinflammation, hallmark neurodegenerative diseases aging, is reported dubious impact on activation, cells pro- anti-inflammatory cytokines chemokines, anti-oxidants, free radicals, neurotrophic factors. Despite emerging evidence supporting reactive duality their phenotype, neurotoxic or neuroprotective properties, depending age stimuli, cellular interplays regional still matter discussion. In this review, we will summarize recent phenotypes, likely for during neural diseases. We focus molecules triggered by Finally, discuss new how modulation phenotype could synaptic deficits dysfunction present pathological states.

Language: Английский

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders DOI
Melanie D. Sweeney, Abhay P. Sagare, Berislav V. Zloković

et al.

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(3), P. 133 - 150

Published: Jan. 29, 2018

Language: Английский

Citations

2279
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? DOI

Fangda Leng,

Paul Edison

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 17(3), P. 157 - 172

Published: Dec. 14, 2020

Language: Английский

Citations

2069
Blood-Brain Barrier: From Physiology to Disease and Back DOI Open Access
Melanie D. Sweeney, Zhen Zhao, Axel Montagne

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 21 - 78

Published: Oct. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Language: Английский

Citations

1670
Clearance systems in the brain—implications for Alzheimer disease DOI

Jenna M. Tarasoff-Conway,

Roxana O. Carare, Ricardo S. Osorio

et al.

Nature Reviews Neurology, Journal Year: 2015, Volume and Issue: 11(8), P. 457 - 470

Published: July 21, 2015

Language: Английский

Citations

1385
The far-reaching scope of neuroinflammation after traumatic brain injury DOI Open Access
Dennis Simon, Mandy J. McGeachy, Hülya Bayır

et al.

Nature Reviews Neurology, Journal Year: 2017, Volume and Issue: 13(3), P. 171 - 191

Published: Feb. 10, 2017

Language: Английский

Citations

885
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

705
New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation DOI Creative Commons
Nava Zisapel

British Journal of Pharmacology, Journal Year: 2018, Volume and Issue: 175(16), P. 3190 - 3199

Published: Jan. 10, 2018

In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of hypothalamus, tunes innate physiological rhythms to ambient 24 h light-dark cycle invigorate and optimize internal temporal order. The SCN-activated, light-inhibited production melatonin conveys message darkness clock induces night-state functions, for example, sleep/wake blood pressure metabolism. Clinically meaningful effects treatment have been demonstrated placebo-controlled trials humans, particularly disorders associated with diminished or misaligned rhythms, rhythm-related sleep disorders, jet lag shift work, insomnia children neurodevelopmental poor (non-restorative) quality, non-dipping nocturnal (nocturnal hypertension) Alzheimer's disease (AD). at very early stages AD, role restorative value (perceived quality) its sleep-anticipating resulting attenuated activation certain brain networks are gaining new perspective as quality build-up β amyloid, precuneus, is unravelled. As result recently discovered relationship between neurodegeneration, prospects using intervention, promote healthy physical mental ageing, prime interest view emerging link aetiology disease. LINKED ARTICLES: This article part themed section on Recent Developments Research Melatonin Potential Therapeutic Applications. To other articles this visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.

Language: Английский

Citations

647
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future DOI

Benjamin A. Plog,

Maiken Nedergaard

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2017, Volume and Issue: 13(1), P. 379 - 394

Published: Dec. 1, 2017

The central nervous system (CNS) is unique in being the only organ lacking lymphatic vessels to assist removal of interstitial metabolic waste products. Recent work has led discovery glymphatic system, a glial-dependent perivascular network that subserves pseudolymphatic function brain. Within pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into interstitium astrocytic aquaporin-4, and then drives perivenous drainage (ISF) its solute. Here, we review role pathway CNS physiology, factors known regulate flow, pathologic processes which breakdown CSF-ISF exchange been implicated disease initiation progression. Important areas future research, including manipulation activity aiming improve clearance therapeutic agent delivery, are also discussed.

Language: Английский

Citations

630
Perivascular spaces in the brain: anatomy, physiology and pathology DOI
Joanna M. Wardlaw, Helene Benveniste,

Maiken Nedergaard

et al.

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(3), P. 137 - 153

Published: Feb. 24, 2020

Language: Английский

Citations

610
Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases DOI
Toshiaki Taoka, Yoshitaka Masutani, Hisashi Kawai

et al.

Japanese Journal of Radiology, Journal Year: 2017, Volume and Issue: 35(4), P. 172 - 178

Published: Feb. 14, 2017

Language: Английский

Citations

592