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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25755

Title: Protein Hypercitrullination, a Basic Mechanism of Demyelinating Diseases
Authors: Lei, Haolan
Advisor: Moscarello, Mario
Department: Laboratory Medicine and Pathobiology
Keywords: multipls sclerosis
citrullination
peptidylarginine deiminases
2-chloro acetamidine
Issue Date: 10-Jan-2011
Abstract: Multiple sclerosis (MS) is a complex disease of the human central nervous system (CNS) involving the patchy destruction of the myelin sheath. Previous studies have found a consistent biochemical change in MS normal appearing white matter (NAWM) i.e. the increased citrullination of myelin basic protein (MBP) resulting in decreased myelin compaction. This process is facilitated by the enzyme family of peptidylarginine deiminases (PADs), of which PAD2 and PAD4 are expressed in mouse and human brain white matter. Therefore, we propose the inhibition of PAD enzymes would reverse protein hypercitrullination and represents a potential treatment for MS. Treatment with 2-chloroacetamidine (2CA), an active site inhibitor of PAD, attenuated diseases in four independent mouse models of MS associated with decreased PAD activity level, normalized peptidylcitrullination, and improved myelin morphology. Therefore, protein hypercitrullination may be a basic mechanism implicated in both neurodegenerative and autoimmune models of MS.
URI: http://hdl.handle.net/1807/25755
Appears in Collections:Master
Department of Laboratory Medicine and Pathobiology - Master theses

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