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Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson's disease.
Xia, Ning; Madore, Victoria; Albalakhi, Ali; Lin, Sonia; Stimpson, Taylor; Xu, Yuehang; Schwarzschild, Michael A; Bakshi, Rachit.
Affiliation
  • Xia N; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA. nxia@mgh.harvard.edu.
  • Madore V; Harvard Medical School, Boston, MA, 02115, USA. nxia@mgh.harvard.edu.
  • Albalakhi A; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
  • Lin S; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
  • Stimpson T; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
  • Xu Y; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
  • Schwarzschild MA; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
  • Bakshi R; Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, MA, 02129, USA.
Sci Rep ; 13(1): 15539, 2023 09 20.
Article in En | MEDLINE | ID: mdl-37730914
ABSTRACT
Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune-responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP+-induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD.
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Full text: 1 Database: MEDLINE Main subject: Parkinson Disease / Neuroprotective Agents / Neurotoxicity Syndromes Type of study: Prognostic_studies Limits: Animals Language: En Year: 2023 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Parkinson Disease / Neuroprotective Agents / Neurotoxicity Syndromes Type of study: Prognostic_studies Limits: Animals Language: En Year: 2023 Type: Article