TY - CHAP
T1 - The multiple sclerosis degradome
T2 - Enzymatic cascades in development and progression of central nervous system inflammatory disease
AU - Scarisbrick, I. A.
PY - 2008
Y1 - 2008
N2 - An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease. Proteolytic events participate in demyelination, axon injury, apoptosis, and development of the inflammatory response including immune cell activation and extravasation, cytokine and chemokine activation/inactivation, complement activation, and epitope spreading. The potential significance of proteolytic activity to MS therefore relates not only to their potential use as important biomarkers of disease activity, but additionally as prospective therapeutic targets. Experimental data indicate that understanding the net physiological consequence of altered protease levels in MS development and progression necessitates understanding protease activity in the context of substrates, endogenous inhibitors, and proteolytic cascade interactions, which together make up the MS degradome. This review will focus on evidence regarding the potential physiologic role of those protease families already identified as markers of disease activity in MS; that is, the metallo-, serine, and cysteine proteases.
AB - An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease. Proteolytic events participate in demyelination, axon injury, apoptosis, and development of the inflammatory response including immune cell activation and extravasation, cytokine and chemokine activation/inactivation, complement activation, and epitope spreading. The potential significance of proteolytic activity to MS therefore relates not only to their potential use as important biomarkers of disease activity, but additionally as prospective therapeutic targets. Experimental data indicate that understanding the net physiological consequence of altered protease levels in MS development and progression necessitates understanding protease activity in the context of substrates, endogenous inhibitors, and proteolytic cascade interactions, which together make up the MS degradome. This review will focus on evidence regarding the potential physiologic role of those protease families already identified as markers of disease activity in MS; that is, the metallo-, serine, and cysteine proteases.
UR - http://www.scopus.com/inward/record.url?scp=39549110822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39549110822&partnerID=8YFLogxK
U2 - 10.1007/978-3-540-73677-6_6
DO - 10.1007/978-3-540-73677-6_6
M3 - Chapter
C2 - 18219817
AN - SCOPUS:39549110822
SN - 9783540736769
T3 - Current Topics in Microbiology and Immunology
SP - 133
EP - 175
BT - Advances in multiple Sclerosis and Experimental Demyelinating Diseases
PB - Springer Verlag
ER -