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LRRK2 as a modulator of lysosomal calcium homeostasis with downstream effects on autophagy

Patricia Gómez-Suaga1, Sabine Hilfiker

  • 1Institute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.

Autophagy
|March 24, 2012
PubMed

Insights

Leucine rich repeat kinase 2 (LRRK2) regulates autophagy and cell survival via calcium signaling. This discovery offers new therapeutic avenues for neurodegenerative diseases like Parkinson disease.

Area of Science:

  • Neurobiology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Autophagy dysregulation is implicated in neurodegenerative diseases, notably Parkinson disease (PD).
  • The Parkinson disease-associated gene, leucine rich repeat kinase 2 (LRRK2), is linked to autophagy, but its precise role is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which LRRK2 influences autophagy.
  • To investigate the role of calcium signaling in LRRK2-mediated autophagy regulation.

Main Methods:

  • Investigated LRRK2's function in cellular models of neurodegeneration.
  • Utilized calcium imaging and autophagy flux assays.
  • Examined the impact of LRRK2 on cell survival pathways.

Main Results:

  • LRRK2 modulates autophagy through calcium-dependent signaling pathways.
  • These calcium events originate from acidic cellular stores.
  • LRRK2 activity impacts cellular survival in the context of autophagy.

Conclusions:

  • LRRK2 regulates autophagy and cell survival via calcium-mediated events from acidic stores.
  • Understanding this mechanism provides a basis for novel therapeutic strategies for Parkinson disease and related disorders.

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