Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis
Abstract
Protein translation is one of the most fundamental and exquisitely controlled processes in biology, and is energetically demanding. The deregulation of this process is deleterious to cells, as demonstrated by several diseases caused by mutations in protein translation machinery. Emerging evidence now points to a role for protein translation in the pathogenesis of Parkinson's disease (PD); a debilitating neurodegenerative movement disorder. In this paper, we propose a hypothesis that protein translation machinery, PD-associated proteins and PD pathology are connected in a functional network linking cell survival to protein translation control. This hypothesis is a potential game changer in the field of the molecular pathogenesis of PD, with implications for the development of PD diagnostics and disease-modifying therapies.
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Defects in mRNA translation are linked to autosomal dominant PD and autosomal recessive PD, where there is aberrant bulk protein synthesis coupled to neurodegeneration.
“Defects in mRNA translation are linked to autosomal dominant PD (5,6) and autosomal recessive PD (7), where there is aberrant bulk protein synthesis that is coupled to neurodegeneration (8,9).”
From Enhanced mTORC1 signaling and Protein Synthesis in Parkinson’s Disease Pathogenesis Disease Pathogenesis (2022) · cites this paper as [9]
Cites
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Activation of the unfolded protein response in Parkinson’s disease
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Autism-related deficits via dysregulated eIF4E-dependent translational control
Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., et al. (2013) · Nature · doi:10.1038/nature11628 · Cited by 522 · see citing works
Signalling to translation: How signal transduction pathways control the protein synthetic machinery
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Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss
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The prion hypothesis in Parkinson's disease: braak to the future
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Khan, M. R., Yin, X., Kang, S.-U., Mitra, J., Wang, H., Ryu, T., Brahmachari, S., Karuppagounder, S. S., Kimura, Y., Jhaldiyal, A., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add0499 · Cited by 64 · see citing works
Khan, M. R., Yin, X., Kang, S.-U., Mitra, J., Wang, H., Brahmachari, S., Karuppagounder, S. S., Kimura, Y., Jhaldiyal, A., Kim, H. H., et al. (2022) · doi:10.1101/2022.10.03.510455
- Authors
- Taymans, J.-M., Nkiliza, A., & Chartier-Harlin, M.-C.
- Affiliations
- Inserm (FR)
- Corresponding author
- Taymans, Jean-Marc
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 21
- Issue
- 8
- Pages
- 466-472
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W1583563962
- Cited by
- 50
- References
- 6
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 11 · 2016: 4 · 2015: 2
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- Parkinson's disease, mRNA translation, translational regulation, neurodegeneration, cell survival, molecular pathogenesis, disease-modifying therapy
- MeSH terms
- Gene Expression Regulation, Humans, Parkinson Disease, Protein Biosynthesis, Genetic Predisposition to Disease, Genetic Association Studies
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