Title:An Overview on the Role of α -Synuclein in Experimental Models of Parkinson’s Disease from Pathogenesis to Therapeutics
Volume: 15
Issue: 10
Author(s): Hayate Javed, Mohammad Amjad Kamal and Shreesh Ojha
Affiliation:
Keywords:
Animal, experimental, models, parkinson’s disease, α-synuclein, neurotoxicity, environmental toxins, neurotoxins.
Abstract: Parkinson's disease (PD) is a devastating and progressive movement disorder characterized
by symptoms of muscles rigidity, tremor, postural instability and slow physical movements.
Biochemically, PD is characterized by lack of dopamine production and its action due to loss of
dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as
Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed
that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy
body. Based on the important role of α-syn from pathogenesis to therapeutics, the recent researches are
mainly focused on deciphering the critical role of α-syn at advanced level. Being a major protein in
Lewy body that has a key role in pathogenesis of PD, several model systems including immortalized
cell lines (SH-SY5Y), primary neuronal cultures, yeast (saccharomyces cerevisiae), drosophila (fruit
flies), nematodes (Caenorhabditis elegans) and rodents are being employed to understand the PD
pathogenesis and treatment. In order to study the etiopathogensis and develop novel therapeutic target
for α -syn aggregation, majority of investigators rely on toxin (rotenone, 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine, 6-hydroxydopamine, paraquat)-induced animal models of PD as a tool for basic
research. Whereas, cell and tissue based models are mostly utilized to elucidate the mechanistic and
molecular pathways underlying the α -syn induced toxicity and therapeutic approaches in PD. Gene
modified mouse models based on α-syn expression are fascinating for modeling familial PD and toxin
induced models provide a suitable approach for sporadic PD. The purpose of this review is to provide a
summary and a critical review of the involvement of α-syn in various in vitro and in vivo models of PD
based on use of neurotoxins as well as genetic modifications.
