The autophagy-lysosomal degradation pathway: role in neurodegenerative disease and therapy

Front Biosci. 2008 Jan 1;13:718-36. doi: 10.2741/2714.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / chemistry
  • Animals
  • Autophagy*
  • Calpain / chemistry
  • Endosomes / metabolism
  • Humans
  • Lysosomes / metabolism
  • Lysosomes / physiology*
  • Models, Biological
  • Nerve Degeneration
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology*
  • Neurodegenerative Diseases / therapy
  • Neurons / metabolism
  • Oxidative Stress
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology*
  • Parkinson Disease / therapy


  • Amyloid beta-Peptides
  • Calpain