Back to Search
Start Over
Lysosomal dysfunction in proteinopathic neurodegenerative disorders: possible therapeutic roles of cAMP and zinc
- 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.
- Subjects :
- 0301 basic medicine
Disease
Review
Protein degradation
Protein aggregation
Models, Biological
lcsh:RC346-429
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Lysosome
cAMP
Extracellular
medicine
Cyclic AMP
Animals
Humans
Amyotrophic lateral sclerosis
EALP
Molecular Biology
lcsh:Neurology. Diseases of the nervous system
Chemistry
MT3
Neurodegenerative Diseases
Hydrogen-Ion Concentration
medicine.disease
Cell biology
Zinc
030104 developmental biology
medicine.anatomical_structure
Psychopharmacology
Lysosomes
Flux (metabolism)
030217 neurology & neurosurgery
Subjects
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