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Front. Neurosci. | doi: 10.3389/fnins.2019.01142

Proteostasis in Cerebral Small Vessel Disease

  • 1Institute for Stroke and Dementia Research (ISD), Germany

Maintaining the homeostasis of proteins (proteostasis) by controlling their synthesis, folding and degradation is a central task of cells and tissues. The gradual decline of the capacity of the various proteostasis machineries, frequently in combination with their overload through mutated, aggregation-prone proteins, is increasingly recognized as an important catalyst of age-dependent pathologies in the brain, most prominently neurodegenerative disorders. A dysfunctional proteostasis might also contribute to neurovascular disease as indicated by the occurrence of excessive protein accumulation or massive extracellular matrix expansion within vessel walls in conditions such as cerebral small vessel disease, a major cause of ischemic stroke, and cerebral amyloid angiopathy. Recent advances in brain vessel isolation techniques and mass spectrometry methodology have facilitated the analysis of cerebrovascular proteomes and fueled efforts to determine the proteomic signatures associated with neurovascular disease. In several studies in humans and mice considerable differences between healthy and diseased vessel proteomes were observed emphasizing the critical contribution of an impaired proteostasis to disease pathogenesis. These findings highlight the important role of a balanced proteostasis for cerebrovascular health.

Keywords: CADASIL, CARASIL, Cerebral Amyloid Angiopathy, HTRA1, Notch3, Proteomics, Chaperone

Received: 07 May 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Haffner. 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: Dr. Christof Haffner, Institute for Stroke and Dementia Research (ISD), Munich, Germany, christof.haffner@med.uni-muenchen.de