Key result
Mutations in multiple DNAJC proteins, including Auxilin, GAK, RME-8, and CSPα, functionally converge on pathways of synaptic trafficking and clathrin dynamics in the pathogenesis of parkinsonism.
Why the study?
DNAJC protein mutations have been linked with parkinsonism, prompting a review of the current genetic and functional evidence connecting these proteins and their mutations to disease pathogenesis.
This review highlights the role of DNAJC proteins in synaptic trafficking and clathrin dynamics, contributing to the pathogenesis of parkinsonism.
Genetic links of DNAJC mutations to parkinsonism remain hypothesis-generating; prospective functional studies needed before clinical implications.
The DNAJC protein family is a subclass of heat shock proteins that has attracted recent attention due to the identification of mutations that are linked with parkinsonism, a feature of Parkinson's disease and other neurological disorders. In this review, we discuss the current genetic and functional evidence of the association of these DNAJC proteins with disease and how mutations in these proteins may contribute to disease pathogenesis. Although DNAJC6 (Auxilin), DNAJC12, and DNAJC5 (CSPα) exhibit strong genetic association with disease, DNAJC26 (GAK), DNAJC13 (RME-8), and DNAJC10 (Erdj5) require additional evidence to definitively link reported variants to parkinsonism. Remarkably, multiple DNAJC proteins (Auxilin, GAK, RME-8, CSPα) functionally converge on pathways of synaptic trafficking and clathrin dynamics, highlighting an important role of those pathways in the pathogenesis of parkinsonism. Further research is required to define the mechanisms through which these mutations contribute to disease etiology.
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Roosen et al. (2019) conducted a review in Parkinsonism. DNAJC protein mutations was evaluated. Mutations in multiple DNAJC proteins, including Auxilin, GAK, RME-8, and CSPα, functionally converge on pathways of synaptic trafficking and clathrin dynamics in the pathogenesis of parkinsonism.
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