Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models. Multiple experimental studies showed the ability of several plant extracts to protect against MPTP induced neurotoxicity through activation of catalase, superoxide dismutase, and glutathione reductase enzymes, which reduce the cellular concentration of free radicals, preventing intracellular Ca++ release and subsequent apoptosis signaling. Other neuroprotective mechanisms of plant extracts include promoting autophagy of alpha-synuclein molecules and exerting an antiapoptotic activity via inhibition of proteolytic poly (ADP-ribose) polymerase and preventing caspase cleavage. The variety of neuroprotective mechanisms of natural plant extracts may allow researchers to target PD progression in different pathological stages and may be through multiple pathways. Further investigations are required to translate these neuroprotective mechanisms into safe and effective treatments for PD.