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PMID: 34182602 Published · aheadofprint English Journal Article

The role of extracellular matrix alterations in mediating astrocyte damage and pericyte dysfunction in Alzheimer's disease: A comprehensive review.

The European journal of neuroscience ·2021-06-28

Anwar MM, Özkan E, Gürsoy-Özdemir Y

Abstract

The brain is a highly vascularized tissue protected by the blood-brain barrier (BBB), a complex structure allowing only necessary substances to pass through into the brain while limiting the entrance of harmful toxins. The BBB comprises several components, and the most prominent features are tight junctions between endothelial cells (ECs), which are further wrapped in a layer of pericytes. Pericytes are multitasked cells embedded in a thick basement membrane (BM) that consists of a fibrous extracellular matrix (ECM) and are surrounded by astrocytic endfeet. The primary function of astrocytes and pericytes is to provide essential blood supply and vital nutrients to the brain. In Alzheimer's disease (AD), long-term neuroinflammatory cascades associated with infiltration of harmful neurotoxic proteins may lead to BBB dysfunction and altered ECM components resulting in brain homeostatic imbalance, synaptic damage, and declined cognitive functions. Moreover, BBB structure and functional integrity may be lost due to induced ECM alterations, astrocyte damage, and pericytes dysfunction, leading to amyloid-beta (Aβ) hallmarks deposition in different brain regions. Herein, we highlight how BBB, ECM, astrocytes, and pericytes dysfunction can play a leading role in AD's pathogenesis and discuss their impact on brain functions.

Keywords
Alzheimer's disease BBB dysfunction astrocytes pericytes basement membrane extracellular matrix
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Anwar Mai M ORCID
Neuroscience Research Lab, Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey. | Department of Biochemistry, National Organization for Drug Control and Research (NODCAR)/Egyptian Drug Authority, Cairo, Egypt.
Özkan Esra ORCID
Neuroscience Research Lab, Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
Gürsoy-Özdemir Yasemin ORCID
Neuroscience Research Lab, Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey. | Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey.
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Article Info
Journal
The European journal of neuroscience
Abbr.
Eur J Neurosci
ISSN
1460-9568
DOI
10.1111/ejn.15372
Published
2021-06-28
Epub
2021-00-28
Language
English
Region
France
NLM ID
8918110
Subset
IM
External Links
PubMed source DOI: 10.1111/ejn.15372 View journal details
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