DNAJC proteins and pathways to parkinsonism
Dorien A Roosen1,2, Cornelis Blauwendraat1, Mark R Cookson1
1Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
The FEBS Journal
|May 24, 2019
Summary
Mutations in DNAJC proteins, heat shock proteins, are linked to parkinsonism. DNAJC6, DNAJC12, and DNAJC5 show strong genetic links, while others need more evidence, highlighting synaptic trafficking
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- DNAJC proteins, a subclass of heat shock proteins, are under investigation for their role in neurological disorders.
- Mutations in specific DNAJC proteins have been genetically linked to parkinsonism, a key feature of Parkinson's disease.
Purpose of the Study:
- To review the genetic and functional evidence associating DNAJC proteins with disease pathogenesis.
- To explore how mutations in DNAJC proteins contribute to the development of parkinsonism.
Main Methods:
- Review of current genetic and functional evidence.
- Analysis of reported variants in DNAJC proteins and their association with parkinsonism.
- Functional convergence analysis on synaptic trafficking and clathrin dynamics pathways.
Main Results:
- DNAJC6 (Auxilin), DNAJC12, and DNAJC5 (CSPα) demonstrate strong genetic associations with disease.
- DNAJC26 (GAK), DNAJC13 (RME-8), and DNAJC10 (Erdj5) require further evidence to confirm their link to parkinsonism.
- Multiple DNAJC proteins converge on synaptic trafficking and clathrin dynamics, implicating these pathways in parkinsonism pathogenesis.
Conclusions:
- The DNAJC protein family plays a significant role in the etiology of parkinsonism.
- Synaptic trafficking and clathrin dynamics are critical pathways in DNAJC-related parkinsonism.
- Further research is needed to elucidate the precise mechanisms linking DNAJC mutations to disease.
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