Objective: The current investigation aimed to investigate the neuroprotective effect of niclosamide (NI) on autophagy and neuroinflammatory pathways in Parkinson’s disease (PD).

Background: Autophagy dysregulation and neuroinflammation are two of the main pathogenic pathways for the onset of PD. NI, a drug approved for the treatment of tapeworm infections, has been found to promote autophagy via mTOR inhibition and show therapeutic potential in neurodegenerative diseases, while its involvement in PD is still unclear.

Method: To develop a PD model, BALB/c mice were given 30 mg/kg/i.p./day of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) for five straight days. The doses of NI (5-10 mg/kg/day/i.p.) were given once daily for 14 days after MPTP poisoning. The animals were observed for behavioral & locomotor activity, oxidative stress markers, proinflammatory cytokine levels, IL-1β &TNF-α, and neuronal autophagy (LC3B & Beclin1) markers.  Additionally, the antioxidant and anti-inflammatory properties of NI were examined in PC12 cells by determining intracellular ROS and cell viability.

Results: NI regulates the autophagy-lysosome pathway, induces autophagy stimulation, and acts as an anti-inflammatory to reduce cerebral inflammation in PD cellular and animal models. NI possesses neurorestorative effects by successfully halting MPTP-induced ROS formation and cell loss. NI reduces behavioral and motor deficits. NI has a neuroprotective impact by successfully rescuing MPTP-induced oxidative stress markers and lowering levels of inflammatory cytokines. Furthermore, NI therapy enhances neuronal autophagy markers in PD mice.

Conclusion: The present research suggests that dysregulation of autophagy and neuroinflammation are involved in the pathogenesis and progression of MPTP-induced PD. NI significantly reduces MPTP-induced PD distortions, indicating that it could be used as a future therapeutic.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-autophagy-and-neuroinflammation-by-niclosamide-in-mptp-induced-parkinsons-disease-model/