Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/169231
Title: Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases
Authors: Lo, Chih Hung
Zeng, Jialiu
Keywords: Science::Medicine
Issue Date: 2023
Source: Lo, C. H. & Zeng, J. (2023). Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases. Translational Neurodegeneration, 12(1), 29-. https://dx.doi.org/10.1186/s40035-023-00362-0
Project: 021207-00001 
021229-00001 
MOH-001147 
Journal: Translational Neurodegeneration 
Abstract: Lysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Multiple genetic factors have been linked to lysosomal de-acidification through impairing the vacuolar-type ATPase and ion channels on the organelle membrane. Similar lysosomal abnormalities are also present in sporadic forms of neurodegeneration, although the underlying pathogenic mechanisms are unclear and remain to be investigated. Importantly, recent studies have revealed early occurrence of lysosomal acidification impairment before the onset of neurodegeneration and late-stage pathology. However, there is a lack of methods for organelle pH monitoring in vivo and a dearth of lysosome-acidifying therapeutic agents. Here, we summarize and present evidence for the notion of defective lysosomal acidification as an early indicator of neurodegeneration and urge the critical need for technological advancement in developing tools for lysosomal pH monitoring and detection both in vivo and for clinical applications. We further discuss current preclinical pharmacological agents that modulate lysosomal acidification, including small molecules and nanomedicine, and their potential clinical translation into lysosome-targeting therapies. Both timely detection of lysosomal dysfunction and development of therapeutics that restore lysosomal function represent paradigm shifts in targeting neurodegenerative diseases.
URI: https://hdl.handle.net/10356/169231
ISSN: 2047-9158
DOI: 10.1186/s40035-023-00362-0
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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