What lysosomes actually tell us about Parkinson's disease?

Ageing Res Rev. 2016 Dec:32:140-149. doi: 10.1016/j.arr.2016.02.008. Epub 2016 Mar 3.

Abstract

Parkinson's disease is a common neurodegenerative disorder of unknown origin mainly characterized by the loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions called Lewy bodies. Lysosomes are dynamic organelles that degrade, in a controlled manner, cellular components delivered via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing amounts of evidence suggest a central role of lysosomal impairment in PD aetiology. This review provides an update on how genetic evidence support this connection and highlights how the neuropathologic and mechanistic evidence might relate to the disease process in sporadic forms of Parkinson's disease. Finally, we discuss the influence of ageing on lysosomal impairment and PD aetiology and therapeutic strategies targeting lysosomal function.

Keywords: Lysosomes; Neurodegeneration; Parkinson’s disease; Therapeutic.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Autophagy / physiology
  • Dopaminergic Neurons / metabolism
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Lewy Bodies / physiology*
  • Lysosomes / physiology*
  • Melanins / metabolism
  • Nerve Degeneration* / metabolism
  • Nerve Degeneration* / physiopathology
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / physiopathology
  • Substantia Nigra / metabolism
  • Vesicular Transport Proteins / genetics

Substances

  • Melanins
  • VPS35 protein, human
  • Vesicular Transport Proteins
  • neuromelanin
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2