Autophagy and Neurodegenerative Diseases

J Korean Neurol Assoc > Volume 27(3); 2009 > Article

Journal of the Korean Neurological Association 2009;27(3): 206-214.

자가포식현상과 신경퇴행병

백진영, 김범생

포천중문의과대학 진단검사의학과교실, 가톨릭대학교의과대학 신경과학교실a

Autophagy and Neurodegenerative Diseases

Jinyoung Pa다

Department of Diagnostic Medicine, College of medicine, Pochon CHA University, Seoul, Korea Department of Neurologya, College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

Autophagy is a highly regulated cellular mechanism that results in the bulk degradation of long-lived proteins and organelles and which seems to be implicated in a variety of physiological and pathological conditions relevant to neurological diseases. The formation of intraneuronal mutant protein aggregates is a characteristic of several human neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, and polyglutamine disorders such as Huntington’s disease (HD). Autophagy is a major clearance pathway for the removal of the mutant huntingtin protein associated with HD, and many other disease-causing, cytoplasmic, aggregate-prone proteins. Autophagy is negatively regulated by the mammalian target of rapamycin (mTOR) and can be induced in all mammalian cell types by the mTOR inhibitor rapamycin. It can also be induced by an mTOR-independent pathway, which has multiple drug targets, involving links between Ca2+-calpain?Gsα and cAMP?Epac?PLC-e?IP3 signaling. Both pathways enhance the process of autophagy. In this review, we describe the various drugs and pathways that induce autophagy that are potential therapeutic approaches for neurodegenerative disorders. Key Words: Autophagy, Neurodegenerative disorders, mTOR, Rapamycin, mTOR-independent pathway