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Updated: Sep 14, 2025

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
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Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

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AHSA1/Hsp90α Complex Facilitates Microglial Mitophagy by Targeting TOMM70 in Parkinson Disease

Liang Shao1, Ji Zhang2, Fan Hu2

  • 1Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang City, China.

The American Journal of Pathology
|July 20, 2025
PubMed

Insights

Heat shock protein 90α (Hsp90α) facilitates microglial mitophagy in Parkinson disease (PD) by targeting TOMM70. Silencing Hsp90α protected against neurodegeneration in a PD mouse model.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Parkinson disease (PD) is a prevalent neurodegenerative disorder with unclear pathology.
  • Microglial mitophagy plays a role in PD pathogenesis, but its mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of microglial mitophagy in Parkinson disease.
  • To elucidate the molecular mechanisms underlying microglial mitophagy in PD.

Main Methods:

  • Established and validated a 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model.
  • Utilized Western blot, immunofluorescence, qRT-PCR, co-immunoprecipitation, ELISA, transmission electron microscopy, and cell viability assays.
  • Investigated the effects of heat shock protein 90α (Hsp90α) silencing and inhibition, and activator of Hsp90 ATPase activity 1 (AHSA1) knockdown.

Main Results:

  • Autophagy was enhanced in MPTP-induced PD mice.
  • Silencing Hsp90α protected against mitophagy and attenuated dopaminergic neuronal death in PD models.
  • The AHSA1/Hsp90α complex was identified to target TOMM70 in microglia, regulating mitophagy.

Conclusions:

  • The AHSA1/Hsp90α complex promotes microglial mitophagy by targeting TOMM70 in Parkinson disease.
  • Targeting the AHSA1/Hsp90α-TOMM70 pathway may offer a therapeutic strategy for PD.

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