The Autophagy Lysosomal Pathway and Neurodegeneration

Cold Spring Harb Perspect Biol. 2020 Mar 2;12(3):a033993. doi: 10.1101/cshperspect.a033993.


The autophagy lysosomal pathway (ALP) is a major mechanism for degrading intracellular macromolecules. The catabolic products can then be used by the cell for energy or as building blocks to make other macromolecules. Since its discovery, a variety of cellular pathways have emerged that target components with varying specificity for lysosomal degradation. Under some circumstances, lysosomes may release their contents into the extracellular space where they may serve signaling or pathogenic functions. The ALP is active in healthy cells, and the level of activity can be regulated by nutrient-sensing and metabolic signaling pathways. The ALP is the primary pathway by which lipids and damaged organelles are degraded and may be the only pathway capable of degrading aggregated proteins. As such, there has been intense interest in understanding the role of the ALP in the accumulation of aggregated misfolded proteins characteristic of many of the major adult-onset neurodegenerative diseases. This review focuses on recent advances in our understanding of the ALP and its potential relationship to the pathogenesis and treatment of neurodegenerative diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Humans
  • Lipids / chemistry
  • Lysosomes / metabolism*
  • Molecular Chaperones / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Pinocytosis
  • Signal Transduction / physiology*


  • Lipids
  • Molecular Chaperones