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PICALM modulates autophagy activity and tau accumulation

Kevin Moreau1, Angeleen Fleming2, Sara Imarisio3

  • 1Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.

Nature Communications
|September 23, 2014
PubMed

Insights

Phosphatidylinositol binding clathrin assembly protein (CALM) influences Alzheimer's disease (AD) pathology by modulating autophagy and tau protein clearance. CALM

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Genome-wide association studies link Alzheimer's disease (AD) risk loci to endocytic trafficking proteins like PICALM/CALM.
  • The precise mechanisms by which these genetic factors contribute to AD pathogenesis remain largely unknown.

Purpose of the Study:

  • To investigate the role of CALM in modulating autophagy and tau protein clearance in Alzheimer's disease.
  • To elucidate how CALM influences cellular processes relevant to AD pathology.

Main Methods:

  • In vitro and in vivo experiments to assess CALM's effect on autophagy.
  • Utilized zebrafish transgenic models to study CALM's impact on tau-mediated toxicity.
  • Examined CALM's regulation of SNARE proteins involved in endocytosis and autophagy.

Main Results:

  • CALM was found to modulate autophagy and alter the clearance of tau protein, a key player in AD.
  • Altered CALM expression in zebrafish models exacerbated tau-related neurotoxicity.
  • CALM regulates the endocytosis of SNAREs, impacting autophagosome formation and degradation.

Conclusions:

  • The Alzheimer's disease genetic risk factor CALM plays a significant role in modulating autophagy.
  • CALM's influence on tau turnover and autophagy presents a potential therapeutic target for Alzheimer's disease.

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