Lysosomal pH Gradient Manipulation

Proposed by etl-backfill

ATP6V1A neurodegeneration market 52% active
Compare across mechanisms →
Composite
46%
Novelty
50%
Feasibility
50%
Impact
—
Mechanistic
50%
Druggability
50%
Safety
50%
Confidence
50%

Mechanistic description

Therapeutic fine-tuning of lysosomal pH through v-ATPase modulation to optimize seed degradation while preventing toxic fragment formation

Mechanism / pathway

  1. ATP6V1A
  2. neurodegeneration

Evidence for (5)

  • ATM loss disrupts the autophagy-lysosomal pathway.

    PMID:32757690 2021 Autophagy

  • Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.

    PMID:30917721 2019 Autophagy

  • Prosapogenin A induces GSDME-dependent pyroptosis of anaplastic thyroid cancer through vacuolar ATPase activation-mediated lysosomal over-acidification.

    PMID:39138191 2024 Cell Death Dis

  • Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.

    PMID:37239976 2023 Int J Mol Sci

  • Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy.

    PMID:35325805 2022 Redox Biol

Evidence against (1)

Evidence matrix

5 supporting 0 contradicting
100% supporting

Supporting

  • ATM loss disrupts the autophagy-lysosomal pathway. PMID:32757690 · 2021 · Autophagy
  • Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis. PMID:30917721 · 2019 · Autophagy
  • Prosapogenin A induces GSDME-dependent pyroptosis of anaplastic thyroid cancer through vacuolar ATPase activation-mediated lysosomal over-acidification. PMID:39138191 · 2024 · Cell Death Dis
  • Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review. PMID:37239976 · 2023 · Int J Mol Sci
  • Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy. PMID:35325805 · 2022 · Redox Biol

Contradicting

No contradicting evidence recorded.

Cite this hypothesis

Cite this hypothesis
Citation

etl-backfill (2026). Lysosomal pH Gradient Manipulation. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062207-b800e5d3-1

BibTeX 
@misc{scidex_hypothesis_hypsda20,
  title        = {Lysosomal pH Gradient Manipulation},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062207-b800e5d3-1},
  note         = {SciDEX artifact hypothesis:hyp-SDA-2026-04-08-gap-pubmed-20260406-062207-b800e5d3-1}
}

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POST /api/scidex/rpc
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    "content_type": "hypothesis",
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