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Erschienen in: Inflammopharmacology 2/2023

30.01.2023 | Original Article

Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson’s disease

verfasst von: Shipra Kartik, Rishi Pal, Manju J. Chaudhary, Rajendra Nath, Madhu Kumar, Monika Binwal, D. U. Bawankule

Erschienen in: Inflammopharmacology | Ausgabe 2/2023

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Abstract

Parkinson's disease (PD) is a neuro-motor ailment that strikes adults in their older life and results in both motor and non-motor impairments. In neuronal and glial cells, PD has recently been linked to a dysregulated autophagic system and cerebral inflammation. Chloroquine (CQ), an anti-malarial drug, has been demonstrated to suppress autophagy in a variety of diseases, including cerebral ischemia, Alzheimer’s disease (AD), and Traumatic brain injury (TBI), while its involvement in PD is still unclear. BALB/c mice were randomly allocated to one of four groups: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), CQ treatment with or without MPTP, or control. The CQ treatment group received CQ (intraperitoneally, 8 mg/kg body weight) after 1 h of MPTP induction on day 1, and it lasted for 7 days. CQ therapy preserves dopamine levels stable, inhibits tyrosine hydroxylase (TH) positive dopaminergic cell death, and lowers oxidative stress. CQ reduces the behavioural, motor, and cognitive deficits caused by MPTP after injury. Furthermore, CQ therapy slowed aberrant neuronal autophagy (microtubule-associated protein-1 light chain 3B; LC3B & Beclin1) and lowered expression levels of the inflammatory cytokines interleukin 1 (IL-1β) and tumour necrosis factor (TNF-α) in the mice brain. In addition, CQ's antioxidant and anti-inflammatory effects were also tested in MPTP-mediated cell death in PC12 cells, demonstrating that CQ has a neurorestorative impact by successfully rescuing MPTP-induced ROS generation and cell loss. Our findings show that CQ’s can help to prevent dopaminergic degeneration and improve neurological function after MPTP intoxication by lowering the harmful effects of neuronal autophagy and cerebral inflammation.
Literatur
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Metadaten
Titel
Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson’s disease
verfasst von
Shipra Kartik
Rishi Pal
Manju J. Chaudhary
Rajendra Nath
Madhu Kumar
Monika Binwal
D. U. Bawankule
Publikationsdatum
30.01.2023
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 2/2023
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-023-01141-z

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