TY - JOUR
T1 - Perlecan and the blood-brain barrier
T2 - Beneficial proteolysis?
AU - Roberts, Jill
AU - Kahle, Michael P.
AU - Bix, Gregory J.
PY - 2012
Y1 - 2012
N2 - The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB), composed of endothelial cells with specialized tight junctions, astrocytes, and a basement membrane (BM). Prominent components of the BM extracellular matrix (ECM) include fibronectin, laminin, collagen IV, and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the BM and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV) of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.
AB - The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB), composed of endothelial cells with specialized tight junctions, astrocytes, and a basement membrane (BM). Prominent components of the BM extracellular matrix (ECM) include fibronectin, laminin, collagen IV, and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the BM and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV) of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.
KW - Blood-brain barrier
KW - Brain
KW - Domain V
KW - Extracellular matrix
KW - Perlecan
KW - Stroke
KW - Vascular basement membrane
UR - http://www.scopus.com/inward/record.url?scp=84866148470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866148470&partnerID=8YFLogxK
U2 - 10.3389/fphar.2012.00155
DO - 10.3389/fphar.2012.00155
M3 - Article
C2 - 22936915
AN - SCOPUS:84866148470
SN - 1663-9812
VL - 3 AUG
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - Article 155
ER -