Unrevealing the molecular mechanisms of MPTP-induced Parkinson's in experimental animals

Parkinson's disease (PD) is the 2nd most prevalent neurodegenerative illness globally, characterized by tremors, stiffness, bradykinesia, and postural imbalances. In PD degradation of dopaminergic neuronal cells in the substantia nigra, results in decreased dopamine levels in the striatum and which is achieved by various neurotoxins and MPTP remain most effective in various animal models. The MPTP-induced rodent model, which has been commonly utilized in PD research because of its practicality and reduced ethical considerations, also replicates all characteristics of human PD. MPTP potentially affects humans, monkeys, rats, zebrafish, and Caenorhabditis elegans. MPTP causes neurotoxicity by forming its toxic metabolite MPP+ through MAO-B (monoamine oxidase B) enzyme and entering into the brain through the dopamine transporter and causing aggregation of alpha-synuclein, inhibition of mitochondrial complex I enzyme, formation of free radicals, release of proinflammatory factors, elevation in glutamate may affect mitochondria, therefore ultimately causing dopaminergic cell death. Recent studies found significant decreases in various neurobehavioural functions, along with low dopamine levels in the brain. The results of recent studies employing this model are excellent. The model has the limitation that chronic MPTP administration causes rapid neuron death and lacks alpha-synuclein aggregation and Lewy formation. Future research should focus on replicating all Parkinsonian symptoms identical to human PD as a focus for therapy.