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Metalloproteinases and neurodegenerative diseases: pathophysiological and therapeutic perspectives

Authors Rosenberg G

Received 26 May 2015

Accepted for publication 23 July 2015

Published 3 September 2015 Volume 2015:2 Pages 39—50


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Sreejesh Shanker

Peer reviewer comments 3

Editor who approved publication: Professor William Parks

Gary A Rosenberg,1–4

1Department of Neurology, 2Department of Neurosciences, 3Department of Cell Biology and Physiology, 4Department of Mathematics and Statistics, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

Abstract: Matrix metalloproteinases (MMPs) are important in the central nervous system from growth and development to brain injury and repair. Cerebral blood vessels are central to the role of the MMPs in the brain. MMPs are a final common pathway for disruption of the blood–brain barrier through proteolysis of the extracellular matrix proteins in the basal lamina surrounding cerebral capillaries and in the unraveling of the essential structure formed by tight-junction proteins that maintain the protected microenvironment necessary for neuronal function. MMPs are major factors in the pathological processes that occur in the brain with hypoxia/ischemic injury, multiple sclerosis, infection, and vascular causes of dementia. In each of these neurological disorders, the MMPs disrupt the blood–brain barrier and damage the myelinated nerve fibers. Inhibitors of MMPs block injury in each of these illnesses in animal models. It is important to develop MMP inhibitors that can be translated from animal studies to human treatments.

Keywords: blood–brain barrier, matrix metalloproteinases, multiple sclerosis, stroke, vascular cognitive impairment, Alzheimer's disease, hypoxia inducible factor-1α

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