Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
September 5, 2025Open Access

Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinsons Disease

View Full Paper
Ask AI
Bookmark
Share

Authors

PSPreethi SheshadriMRC Laboratory for Molecular Cell BiologyMCMaria A. Costa-BesadaUniversidade de Santiago de CompostelaAFAndrew J. FisherUniversity of California, Davis

Discussion

Loading...

Member takes

Overview

Observational analysis reveals that lysosomal acidification improves mitophagy in GBA1-related Parkinson's disease, suggesting a new therapeutic target.

Key Points

  • Impaired lysosomal acidification leads to dysfunctional mitophagy and mitochondrial bioenergetics in GBA1 mutant cells.
  • Treatment with rapamycin increased V-ATPase assembly, restoring lysosomal pH and improving mitochondrial function.
  • Using acidic nanoparticles successfully normalized lysosomal pH and mitophagy in affected dopaminergic neurons.
  • Targeting lysosomal pathways may provide a novel therapeutic approach for GBA1-mediated Parkinson's disease.

Cite This Study

Sheshadri et al. (2025) studied this question.

synapsesocial.com/papers/68bb5f266d6d5674bcd02f67https://doi.org/10.1101/2025.08.28.672738
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism2023 · 90 citations
  2. 2The crucial impact of lysosomes in aging and longevity2016 · 256 citations
  3. 3Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor2020 · 98 citations
  4. 4Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease2009 · 2,176 citations
  5. 5mTOR coordinates protein synthesis, mitochondrial activity and proliferation2015 · 589 citations