Dose-related biphasic effect of the Parkinson's disease neurotoxin MPTP, on the spread, accumulation, and toxicity of α-synuclein.

Background: Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, is characterized by the abnormal accumulation of intraneuronal inclusions enriched in aggregated α-synuclein (α-syn), known as Lewy bodies (LBs) and Lewy neurites (LNs), and significant loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the brain. Recent evidence suggests that the intrastriatal inoculation of α-syn preformed fibrils (PFF) in mice brain triggers endogenous α-syn in interconnected brain regions. 1-methyl, 4-phenyl, 1,2,3,6 tetrahydropyridine (MPTP), a mitochondrial neurotoxin, has been used previously to generate a PD mouse model.

Thymoquinone prevents neurodegeneration against MPTP in vivo and modulates α-synuclein aggregation in vitro.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive dopaminergic neurodegeneration with a concomitant increase in oxidative stress and neuroinflammation in the substantia nigra pars compacta (SNc). Recent studies have focused on targeting neuroinflammation and oxidative stress to effectively treat PD. The present study evaluated the neuroprotective effect of thymoquinone (TQ) against 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced oxidative stress and neuroinflammation in a PD mouse model.