Transglutaminase-Catalyzed Crosslinking in Neurological Disease: From Experimental Evidence to Therapeutic Inhibition

E-ISSN： 1996-3181|9|2|217-231

ISSN： 1871-5273

Source： CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders), Vol.9, Iss.2, 2010-04, pp. : 217-231

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Abstract

Diseases of polyglutamine expansion, Alzheimer's disease and Parkinson's disease are neurodegenerative diseases associated with insoluble protein aggregates and neuronal death. These diseases constitute a group of devastating diseases for which there is currently little treatment. The protein aggregates may be the cause of neuronal death, although there is some controversy as to which form of aggregation (oligomers, polymers or microscopic aggregates) is the most toxic. More than a decade ago, the participation of transglutaminases in the formation of the abnormal protein aggregates was proposed. Transglutaminases are a large family of enzymes that catalyze the formation of Nε(&ggr;-glutamyl)-lysine isodipeptide crosslinks between proteins. In this review, we summarize the evidence supporting the participation of transglutaminase in diseases of the central nervous system. We also describe newly developed transglutaminase inhibitors and their potential use as therapeutic agents in neurological disease.