Lysosomal alkalinization: a convergent mechanism in lysosomal storage disorders and classical neurodegenerative diseases
4 affiliations
- 1Department of Ophthalmology, University of Rochester, NY Rochester, 14620 USA
- 2Center for Visual Science, University of Rochester, Rochester, NY 14620 USA
- 3Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620 USA
- 4University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 USA
Abstract
Lysosomes are important cellular organelles involved in the recycling of biomolecules in the cell. The acidic intraluminal pH of the lysosome is necessary for the functioning of various hydrolytic enzymes involved in the recycling of biomolecules. Elevated lysosomal pH has been consistently documented in pathological conditions associated with progressive neurodegeneration, including several classical neurodegenerative diseases (e.g., Alzheimer’s disease, Huntington’s disease) and lysosomal storage disorders or LSDs (e.g., Gaucher disease, CLN3 disease). This review focuses on the molecular mechanisms of lysosomal pH regulation, describing the critical roles of vacuolar ATPases and ion channels in maintaining lysosomal pH homeostasis. Further, we highlight how defective acidification of the lysosome can promote common cellular defects linked with both classical neurodegeneration and LSDs. The review also draws a parallel between the pathological consequences of experimentally-induced lysosomal alkalinization and two complex classes of disorders: classical neurodegeneration and LSDs. This comparison raises the possibility that lysosomal pH is one of the multiple shared contributing mechanisms for both conditions and, therefore, a conceivable therapeutic target of classical neurodegeneration and LSDs.
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BibTeX
@article{dubey2026lysosomal,
title = {{Lysosomal alkalinization: a convergent mechanism in lysosomal storage disorders and classical neurodegenerative diseases}},
author = {Ankur Rakesh Dubey and Saurabh Kumar and Ruchira Singh},
journal = {Cell Communication and Signaling : CCS},
year = {2026},
month = aug,
doi = {10.1186/s12964-026-03118-1},
url = {https://doi.org/10.1186/s12964-026-03118-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Lysosomal alkalinization: a convergent mechanism in lysosomal storage disorders and classical neurodegenerative diseases
AU - Ankur Rakesh Dubey
AU - Saurabh Kumar
AU - Ruchira Singh
PY - 2026
DA - 2026/08/08
JO - Cell Communication and Signaling : CCS
DO - 10.1186/s12964-026-03118-1
UR - https://doi.org/10.1186/s12964-026-03118-1
AB - Lysosomes are important cellular organelles involved in the recycling of biomolecules in the cell. The acidic intraluminal pH of the lysosome is necessary for the functioning of various hydrolytic enzymes involved in the recycling of biomolecules. Elevated lysosomal pH has been consistently documented in pathological conditions associated with progressive neurodegeneration, including several classical neurodegenerative diseases (e.g., Alzheimer’s disease, Huntington’s disease) and lysosomal storage disorders or LSDs (e.g., Gaucher disease, CLN3 disease). This review focuses on the molecular mechanisms of lysosomal pH regulation, describing the critical roles of vacuolar ATPases and ion channels in maintaining lysosomal pH homeostasis. Further, we highlight how defective acidification of the lysosome can promote common cellular defects linked with both classical neurodegeneration and LSDs. The review also draws a parallel between the pathological consequences of experimentally-induced lysosomal alkalinization and two complex classes of disorders: classical neurodegeneration and LSDs. This comparison raises the possibility that lysosomal pH is one of the multiple shared contributing mechanisms for both conditions and, therefore, a conceivable therapeutic target of classical neurodegeneration and LSDs.
SN - 1478-811X
ER -