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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00778

Combating Vascular and Neurodegenerative Disorders—Role of DNA Damage and Repair in the Aging Neurovascular Unit

 Yan Li1,  Lv Xie1,  Tingting Huang1, Yueman Zhang1, Jie Zhou1, Bo Qi1, Xin Wang1,  Zengai Chen2 and  Peiying Li1*
  • 1Department of Anesthesiology, Renji Hospital, Shanghai JiaoTong University School of Medicine, China
  • 2Department of Radiology, Renji Hospital, Shanghai JiaoTong University School of Medicine, China

Progressive neurological deterioration poses enormous burden on the aging population with ischemic stroke and neurodegenerative disease patients, such as Alzheimers’ disease and Parkinson’s disease. The past two decades have witnessed remarkable advances in the research of neurovascular unit dysfunction, which is emerging as an important pathological feature that underlies these neurological disorders. Dysfunction of the unit allows penetration of blood-derived toxic proteins or leukocytes into the brain and contributes to white matter injury, disturbed neurovascular coupling and neuroinflammation, which all eventually lead to cognitive dysfunction. Recent evidences suggest that aging-related oxidative stress, accumulated DNA damage and impaired DNA repair capacities compromises the genome integrity not only in neurons, but also in other cell types of the neurovascular unit, such as endothelial cells, astrocytes and pericytes. Combating DNA damage or enhancing DNA repair capacities in the neurovascular unit represents a promising therapeutic strategy for vascular and neurodegenerative disorders. In this review, we focus on aging related mechanisms that underlie DNA damage and repair in the neurovascular unit and introduce several novel strategies that target the genome integrity in the neurovascular unit to combat the vascular and neurodegenerative disorders in the aging brain.

Keywords: Aging, Neurovascular unit (NVU), cerebral ischemia, DNA Damage, DNA Repair, Blood Brain Barrier (BBB)

Received: 30 Mar 2019; Accepted: 11 Jul 2019.

Edited by:

Gregory J. Bix, University of Kentucky, United States

Reviewed by:

Kazuhide Hayakawa, Department of Radiology, Massachusetts General Hospital, United States
Ken Arai, Massachusetts General Hospital and Harvard Medical School
Ana M. Ledo, University of Coimbra, Portugal
Josephine Lok, Massachusetts General Hospital, Harvard Medical School, United States  

Copyright: © 2019 Li, Xie, Huang, Zhang, Zhou, Qi, Wang, Chen and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Peiying Li, Department of Anesthesiology, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China, peiyingli.md@gmail.com