Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy.

Abstract

Neurodegenerative diseases, such as Alzheimer's disease Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, share a common cellular and molecular pathogenetic mechanism involving aberrant misfolded protein or peptide aggregation and deposition. Autophagy represents a major route for degradation of aggregated cellular proteins and dysfunctional organelles. Emerging studies have demonstrated that up-regulation of autophagy can lead to decreased levels of these toxic aggregate-prone proteins, and is beneficial in the context of aging and various models of neurodegenerative diseases. Understanding the signaling pathways involved in the regulation of autophagy is crucial to the development of strategies for therapy. This review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and neurodegenerative diseases, and the ongoing drug discovery strategies for therapeutic modulation.

• Authors: Chen-Chen Tan, Jin-Tai Yu, Meng-Shan Tan, Teng Jiang, Xi-Chen Zhu, Lan Tan
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 35 Issue 5 Pg. 941-57 (May 2014) ISSN: 1558-1497 [Electronic] United States
• PMID: 24360503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• TOR Serine-Threonine Kinases

Topics

• Aging (genetics, pathology)
• Autophagy (genetics, physiology)
• Molecular Targeted Therapy
• Neurodegenerative Diseases (genetics, pathology, therapy)
• Neurons (pathology, physiology)
• Signal Transduction (genetics, physiology)
• TOR Serine-Threonine Kinases (physiology)