MPTP-induced mouse model of Parkinson’s disease: A promising direction of therapeutic strategies

Abstract

Amongst the popular animal models of Parkinson’s disease (PD) commonly used in researches are those that employ neurotoxins, especially the 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). MPTP neurotoxin exerts its neurotoxicity by causing a barrage of insults such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert. All of this ultimately leads to dopaminergic neuron damage in substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neuron of the mouse brain brought a new dawn in our perspectives about PD. For decades now MPTP-induced mouse model of PD has become the gold standard in PD research despite its shortcoming in fully recapitulating PD symptomatology. It has the advantage of easy practicability, affordability, less ethical consideration, and more clinical correlation over the other toxin models of PD. The model has rejuvenated researches in PD and has also opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the MPTP’s role in producing Parkinson-like symptoms in mice, the MPTP-induced mouse model’s experimental role, and the recent development in PD therapeutics using this model to enrich our existing knowledge on this neurotoxin. Furthermore, our review promotes the use of this model by researchers for developing more promising therapeutic strategies.

Mitochondrial CHCHD2: Disease-Associated Mutations, Physiological Functions, and Current Animal Models

“…Mitochondrial dysfunction is a major hallmark of neurodegenerative disease, including synucleinopathies, such as MSA, PD, PDD, and DLB. Over the past 47 years, human and animal studies have shown that the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I inhibitor, induces parkinsonian-like symptoms associated with the loss of DA neurons (Langston et al, 1983;Kopin and Markey, 1988;Kopin, 1992;Langston, 2017;Mat Taib and Mustapha, 2020). Such studies have cemented the link between mitochondrial dysfunction and PD.…”

Elucidating the Neuroprotective Role of PPARs in Parkinson’s Disease: A Neoteric and Prospective Target

“…The neurotoxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was initially recognized to be related to nigrostriatal degeneration, following the emergence of characteristic manifestations of PD in several individuals upon self-administration of narcotic substances contaminated with MPTP. MPTP is bio transformed into an active toxic metabolite named 1-methyl-4-phenylpyridinium ion (MPP+), which belongs to the family of mitochondrial complex-I suppressors, and is exclusively involved in devastating DArgic nerve cells within the SN [ 106 , 107 ]. The exploration of MPTP as a triggering factor for degeneration within the SN encouraged the postulation that PD might be precipitated by toxic substances present in the environment [ 108 ].…”

Implications of Gut Microbiota in Neurodegenerative Diseases

“…Based on the aforementioned findings, we speculate that controversial experimental results were obtained because of the limited pathogenesis of ND mouse models. Human ND etiologies are quite intricate, involving long-term manifold metabolic disorders, gut microbiota alteration, gene mutation, and various hereditary factors, whereas most mouse model etiologies rely on gene editing or medical injection, which might lead to inconsistent pathogenic processes ( 24 , 193 – 201 ). Third, studies have demonstrated that microbiota altered with aging; yet, no evidence is available to confirm whether the altered microflora is healthy, unhealthy, stable, or vulnerable ( 10 , 15 , 22 , 113 , 202 ).…”