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Lysosomal dysfunction in proteinopathic neurodegenerative disorders: possible therapeutic roles of cAMP and zinc

Authors :
Jung Jin Hwang
Sang Eun Park
Jae-Young Koh
Ha Na Kim
Yang-Hee Kim
Source :
Molecular Brain, Vol 12, Iss 1, Pp 1-11 (2019), Molecular Brain
Publication Year :
2019
Publisher :
BMC, 2019.

Abstract

A number of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, share intra- and/or extracellular deposition of protein aggregates as a common core pathology. While the species of accumulating proteins are distinct in each disease, an increasing body of evidence indicates that defects in the protein clearance system play a crucial role in the gradual accumulation of protein aggregates. Among protein degradation systems, the endosome-autophagosome-lysosome pathway (EALP) is the main degradation machinery, especially for large protein aggregates. Lysosomal dysfunction or defects in fusion with vesicles containing cargo are commonly observed abnormalities in proteinopathic neurodegenerative diseases. In this review, we discuss the available evidence for a mechanistic connection between components of the EALP-especially lysosomes-and neurodegenerative diseases. We also focus on lysosomal pH regulation and its significance in maintaining flux through the EALP. Finally, we suggest that raising cAMP and free zinc levels in brain cells may be beneficial in normalizing lysosomal pH and EALP flux.

Details

Language :
English
ISSN :
17566606
Volume :
12
Issue :
1
Database :
OpenAIRE
Journal :
Molecular Brain
Accession number :
edsair.doi.dedup.....c4737362e40613b1ef1ef1c3f5988ef5
Full Text :
https://doi.org/10.1186/s13041-019-0439-2