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DNAJC proteins and pathways to parkinsonism
Author(s) -
Roosen Dorien A.,
Blauwendraat Cornelis,
Cookson Mark R.,
Lewis Patrick A.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14936
Subject(s) - parkinsonism , chemistry , computational biology , microbiology and biotechnology , biology , medicine , disease
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 DNAJC 6 (Auxilin), DNAJC 12 , and DNAJC 5 ( CSP α) exhibit strong genetic association with disease, DNAJC 26 ( GAK ), DNAJC 13 ( RME ‐8), and DNAJC 10 (Erdj5) require additional evidence to definitively link reported variants to parkinsonism. Remarkably, multiple DNAJC proteins (Auxilin, GAK , RME ‐8, CSP α) 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.