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.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- CQ:
-
Chloroquine
- LC3B:
-
Microtubule-associated protein-1 light chain 3B
- MPTP:
-
1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride
- 3-MA:
-
3-Methyladenine
- PD:
-
Parkinson disease
- ROS:
-
Reactive oxygen species
- SNpc:
-
Substantia nigra pars compacta
- TNF-α:
-
Tumour necrosis factor
- TH:
-
Tyrosine hydroxylase
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Acknowledgements
The authors thank the Indian Council of Medical Research (ICMR), New Delhi and research committee of King George's Medical University's for supporting this work.
Funding
The Indian Council of Medical Research (ICMR), New Delhi, India, awarded Ms. Shipra Kartik a senior research fellowship (Project-3/1/2/99/Neuro/2018-NCD-I).
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The experiment was devised by SK and RP. SK performed all of the experiments and wrote the manuscript with the help of MJC, under the guidance of RP. MK assisted with the pathological analysis and RN provided a Technical advice. DUB and MB help in cellular model studies.
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Kartik, S., Pal, R., Chaudhary, M.J. et al. Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson’s disease. Inflammopharmacol 31, 927–941 (2023). https://doi.org/10.1007/s10787-023-01141-z
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DOI: https://doi.org/10.1007/s10787-023-01141-z