ArticleiScience2024
Rebalance of mitophagy by inhibiting LRRK2 improves colon alterations in an MPTP
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration Hampered Contractile Response of Dopamine in Isolated Rat Ileum.Biomedicines · 2025Article
- Mild Chronic Colitis Exacerbates Intracerebral Inflammation in Mice with Parkinson's Disease Through LRRK2-Mediated Regulation of NF-κB Activation and Inhibition of Nrf2.Journal of inflammation research · 2025Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are common genetic causes of Parkinson's disease (PD). Studies demonstrated that variants in LRRK2 genetically link intestinal disorders to PD. We aimed to evaluate whether the selective inhibitor of LRRK2, PF-06447475 (PF-475), attenuates the PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in central nervous system (CNS) and in the gastrointestinal system. CD1 mice received four intraperitoneal injections of MPTP (20 mg/kg, total dose of 80 mg/kg) at 2 h intervals (day 1). After 24 h PF-475 was administered intraperitoneally at the doses of 2.5, 5, and 10 mg/kg for seven days. LRRK2 inhibition reduced brain α-synuclein and modulated mitophagy pathway and reduced pro-inflammatory markers and α-synuclein aggregates in colonic tissues through the modulation of mitophagy proteins. LRRK2 inhibition suppressed MPTP-induced enteric dopaminergic neuronal injury and protected tight junction in the colon. Results suggested that PF-475 may attenuate gastrointestinal dysfunction associated to PD.
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Registered trials
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