Synergetic effect of taurine/taurine nanoparticles along with Sinemet® against rotenone-induced Parkinson’s disease in mice

Parkinson's disease (PD) is a progressive disorder that affects its patients' life quality due to the loss of dopaminergic (DAergic) neurons of <i>substantia nigra</i> (SN), and development of Lewy bodies (LBs) mediated by accumulation of alpha-synuclein (α-Syn) in the brain, causing progressive neuronal loss, and locomotor impairments such as tremor, rigidity, and postural instability. Various pathological factors impact PD progression, such as oxidative stress, neuroinflammation, and kinase activity alterations. This study aimed to evaluate the neuroprotective impacts of Taurine and Taurine nanoparticles (TRN-NPs) alone or along with Sinemet® tablets (ST), investigating their role in attenuating striatal neurodegeneration induced by Rotenone (ROT), a pesticide used to replicate PD-like phenotypes. The study animals were 70 mice, categorized into 10 groups: G1: Normal control, G2: ST control, G3: Taurine control, G4: TRN-NPs control, G5: ROT-induced PD, G6: ROT+ST, G7: ROT+Taurine, G8: ROT+TRN-NPs, G9: ROT+ST + Taurine, and G10: ROT+ST + TRN-NPs. Evaluation of motor function, analysis of brain oxidative stress, pro-inflammatory mediators, and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) activity, along with assessment of gene expression of tyrosine hydroxylase (TH) and synuclein alpha interacting protein (SNCAIP), were performed. The obtained results showed that both Taurine and TRN-NPs improved antioxidant activity, alleviated neuroinflammation, modulated p-ERK1/2 levels, and exhibited marked neuroprotective characteristics observed via histopathological examination of striatum tissue; these effects were more promising in combined treatment groups, which illustrates that the co-administration of TRN-NPs with ST yields a more effective synergistic impact in alleviating ROT-induced Parkinsonian pathologies than monotherapies, indicating a potential viable combinatorial approach for PD management.