J Korean Neurol Assoc.  2009 Aug;27(3):206-214.

Autophagy and Neurodegenerative Diseases

Affiliations
  • 1Department of Diagnostic Medicine, College of medicine, Pochon CHA University, Seoul, Korea.
  • 2Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea. kbs@catholic.ac.kr

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-Gsa 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.

Keyword

Autophagy; Neurodegenerative disorders; mTOR; Rapamycin; mTOR-independent pathway

MeSH Terms

Alzheimer Disease
Autophagy
Cytoplasm
Humans
Huntington Disease
Mutant Proteins
Neurodegenerative Diseases
Organelles
Parkinson Disease
Peptides
Proteins
Sirolimus
Mutant Proteins
Peptides
Proteins
Sirolimus
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