Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration

Neurotherapeutics. 2019 Jul;16(3):611-634. doi: 10.1007/s13311-019-00742-3.


Lysosomes are acidic, membrane-bound organelles that serve as the primary catabolic compartment of the cell. They are crucial to a variety of cellular processes from nutrient storage to autophagy. Given the diversity of lysosomal functions, it is unsurprising that lysosomes are also emerging as important players in aging. Lysosomal dysfunction is implicated in several aging-related neurodegenerative diseases including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis/frontotemporal dementia, and Huntington's. Although the precise role of lysosomes in the aging brain is not well-elucidated, some insight into their function has been gained from our understanding of the pathophysiology of age-dependent neurodegenerative diseases. Therapeutic strategies targeting lysosomes and autophagic machinery have already been tested in several of these diseases with promising results, suggesting that improving lysosomal function could be similarly beneficial in preserving function in the aging brain.

Keywords: Lysosome; aging; autophagy; neurodegeneration; therapeutic targets.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Aging / physiology
  • Amyotrophic Lateral Sclerosis / metabolism
  • Brain / metabolism*
  • Brain / physiology
  • Frontotemporal Dementia / metabolism
  • Humans
  • Huntington Disease / metabolism
  • Lysosomes / physiology*
  • Mitochondria / metabolism
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / prevention & control
  • Parkinson Disease / metabolism