The autophagy-lysosomal degradation pathway: role in neurodegenerative disease and therapy.
Alterations in the autophagy-lysosomal degradation pathway have been described in normal brain aging and in age-related neurodegenerative diseases including Alzheimer's (AD) and Parkinson's (PD). An improper clearance of proteins in AD and PD may result either from a compromise in the autophagy-lysosomal degradation pathway or induce alterations in this pathway, and may result in neuron dysfunction and neuron loss. This review provides an overview of AD and PD with a specific focus on macroautophagy, chaperone-mediated autophagy and lysosome function in human and experimental models of AD and PD. Potential therapies for AD and PD are also discussed that may promote survival by regulating the autophagy and lysosomal degradation pathway.
Shacka
John J
JJ
Division of Neuropathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. shacka@uab.edu
Roth
Kevin A
KA
Zhang
Jianhua
J
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D001343:Autophagy; D002154:Calpain / Q000737:chemistry; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009410:Nerve Degeneration; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy
D016229:Amyloid beta-Peptides; D002154:Calpain