[feed] Atom [feed] RSS 1.0 [feed] RSS 2.0

Kumar, Roshan and Kumar, Sanjay and Hanpude, Pranita and Singh, Abhishek Kumar and Johari, Tanu and Majumder, Sushanta and Maiti, Tushar Kanti (2019) Partially oxidized DJ-1 inhibits α-synuclein nucleation and remodels mature α-synuclein fibrils in vitro. Communications Biology, 2 (1). ISSN 2399-3642

Partially oxidized DJ-1 inhibits α-synuclein.pdf

Download (3546Kb) | Preview


DJ-1 is a deglycase enzyme which exhibits a redox-sensitive chaperone-like activity. The partially oxidized state of DJ-1 is active in inhibiting the aggregation of α-synuclein, a key protein associated with Parkinson’s disease. The underlying molecular mechanism behind α-synuclein aggregation inhibition remains unknown. Here we report that the partially oxidized DJ-1 possesses an adhesive surface which sequesters α-synuclein monomers and blocks the early stages of α-synuclein aggregation and also restricts the elongation of α-synuclein fibrils. DJ-1 remodels mature α-synuclein fibrils into heterogeneous toxic oligomeric species. The remodeled fibers show loose surface topology due to a decrease in elastic modulus and disrupt membrane architecture, internalize easily and induce aberrant nitric oxide release. Our results provide a mechanism by which partially oxidized DJ-1 counteracts α-synuclein aggregation at initial stages of aggregation and provide evidence of a deleterious effect of remodeled α-synuclein species generated by partially oxidized DJ-1.

Item Type: Article
Subjects: Biomedical Science
Biochemical and Biophysical Sciences
Depositing User: RCB Library
Date Deposited: 14 Mar 2023 09:56
Last Modified: 14 Mar 2023 09:56
URI: http://rcb.sciencecentral.in/id/eprint/258

Actions (login required)

View Item View Item