蛋白酶体在信号转导和神经退行性疾病中的作用_英文_.docVIP

183 Neurosci Bull June 1, 2008, 24(3: 183-194. DOI: 10.1007/s12264-008-1029-y ·Original Article· The roles of the proteasome pathway in signal transduction and neurodegenerative diseases Jiao-Jiao CHEN, Fang LIN, Zheng-Hong QIN Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine,Suzhou 215123 Corresponding author: Zheng-Hong QIN Tel: 86-512ax: 86-512E-mail: zhqin5@ Article ID: 1673-7067(200803-0183-012CLC number: Q253Document code: A Received date: 2007-10-29 Abstract : There are two degradation systems in mammalian cells, autophagy/lysosomal pathway and ubiquitin-proteasome pathway. Proteasome is consist of multiple protein subunits and plays important roles in degradation of short-lived cellular proteins. Recent studies reveal that proteasomal degradation system is also involved in signal transduction and regulation of various cellular functions. Dysfunction or dysregulation of proteasomal function may thus be an important pathogenic mechanism in certain neurological disorders. This paper reviews the biological functions of proteasome in signal transduction and its potential roles in neurodegenerative diseases. Keywords : proteasome; signal transduction; protein misfolding; neurodegenerative disease 1 Introduction The integrity of cellular processes depends on the proper balance of synthesis and degradation of cellular proteins.Controlling protein half-life by degradation has emerged as a main cellular mechanism to maintain cellular homeostasis.There are two major degradation pathways involving either a collection of proteolytic enzymes within the lysosome or the multicatalytic proteolytic core of the ubiquitin-proteasome system (UPS. The UPS degrades intracellular proteins with a tag of polyubiquitin chain. In addition to protein degradation,the UPS also plays important roles in diverse physiological functions and pathogenesis in many diseases. Abnormali-ties of UPS have been found in