Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases

Paula Grammas; Joseph Martinez; Bradley Miller

doi:10.1017/S1462399411001918

Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases

Published online by Cambridge University Press: 10 June 2011

Paula Grammas ,

Joseph Martinez and

Bradley Miller

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Paula Grammas*: Affiliation:
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Joseph Martinez: Affiliation:
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Bradley Miller: Affiliation:
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
*: *Corresponding author: Paula Grammas, Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street Stop 9424, Lubbock, TX 79430, USA. E-mail: paula.grammas@ttuhsc.edu

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Abstract

Diseases of the central nervous system (CNS) pose a significant health challenge, but despite their diversity, they share many common features and mechanisms. For example, endothelial dysfunction has been implicated as a crucial event in the development of several CNS disorders, such as Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, multiple sclerosis, human immunodeficiency virus (HIV)-1-associated neurocognitive disorder and traumatic brain injury. Breakdown of the blood–brain barrier (BBB) as a result of disruption of tight junctions and transporters, leads to increased leukocyte transmigration and is an early event in the pathology of these disorders. The brain endothelium is highly reactive because it serves as both a source of, and a target for, inflammatory proteins and reactive oxygen species. BBB breakdown thus leads to neuroinflammation and oxidative stress, which are implicated in the pathogenesis of CNS disease. Furthermore, the physiology and pathophysiology of endothelial cells are closely linked to the functioning of their mitochondria, and mitochondrial dysfunction is another important mediator of disease pathology in the brain. The high concentration of mitochondria in cerebrovascular endothelial cells might account for the sensitivity of the BBB to oxidant stressors. Here, we discuss how greater understanding of the role of BBB function could lead to new therapeutic approaches for diseases of the CNS that target the dynamic properties of brain endothelial cells.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e19

DOI: https://doi.org/10.1017/S1462399411001918 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2011

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Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases

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Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases

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