DJ-1/PARK7: A New Therapeutic Target for Neurodegenerative Disorders

DJ-1, encoded in a causative gene of familial Parkinson’s disease (PARK7), has multiple functions: it works as an antioxidant, in transcriptional regulation, as a molecular chaperone and in protein degradation. Three types of pathogenic mutants of DJ-1 (M26I, D149A and L166P) have been reported to d...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2017/05/01, Vol.40(5), pp.548-552
Main Authors: Hijioka, Masanori, Inden, Masatoshi, Yanagisawa, Daijiro, Kitamura, Yoshihisa
Format: Article
Language:English
Subjects:
Animal models
Animals
Antiparkinson Agents - therapeutic use
Biodegradation
Chemical compounds
Cysteine
DJ-1
DJ-1-binding compound
Gene regulation
Humans
Ischemia
Mutants
Neurodegenerative diseases
Neurodegenerative Diseases - drug therapy
Neurodegenerative Diseases - genetics
neurodegenerative disorder
Oxidation
PARK7 protein
Parkinson Disease - drug therapy
Parkinson Disease - genetics
Parkinson's disease
Protein Deglycase DJ-1 - drug effects
Protein Deglycase DJ-1 - genetics
Proteolysis
Rats
Rodents
Stroke
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Summary:DJ-1, encoded in a causative gene of familial Parkinson’s disease (PARK7), has multiple functions: it works as an antioxidant, in transcriptional regulation, as a molecular chaperone and in protein degradation. Three types of pathogenic mutants of DJ-1 (M26I, D149A and L166P) have been reported to disrupt proper structures and lead to a loss of function. DJ-1 receives oxidation at the cysteine residue, and the degree of oxidation at the C106 residue determines DJ-1 activity. In this decade, DJ-1 has been reported to suppress the progression of various neurodegenerative disorders in animal models. The administration of recombinant wild-type DJ-1 protein suppresses the neuronal loss associated with both Parkinson’s disease and ischemic stroke in rats. Furthermore, in studies focused on DJ-1 as the therapeutic target, compounds that have the capacity of binding to DJ-1 at the C106 residue have been reported to exert therapeutic effects on various neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and ischemic stroke. DJ-1 and DJ-1-targeting molecules/compounds will be useful therapeutic targets for various neurodegenerative disorders due to their various functions such as antioxidant capacity, chaperone function and as a proteolytic pathway.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b16-01006