Imagine you’re baking a cake and you add two different ingredients that react with each other in a unique way. In this study, researchers investigated the effects of injecting fibrils formed by α–Syn and tau fragments into the rat nigrostriatal system, aiming to understand the intricacies of Parkinson’s Disease. They found that these complexes interacted strongly with each other, leading to an accumulation of α-synuclein. As time went on, the rats showed an increase in the amount of α-synuclein deposits in their brains and experienced neurodegeneration. What’s fascinating is that impairments in axonal transport were observed before the neurons died. This finding suggests that disruptions in the transportation system within brain cells could play a pivotal role in Parkinson’s disease progression. This research provides a valuable rat model for studying the mechanisms underlying Parkinson’s disease and testing potential new therapies. If you’re hungry for more knowledge, check out the link below for the full research article!

IntroductionAccurate demonstration of phosphorylated α-synuclein aggregation and propagation, progressive nigrostriatal degeneration and motor deficits will help further research on elucidating the mechanisms of Parkinson’s Disease. α-synucleinN103 and tauN368, cleaved by activated asparagine endopeptidase in Parkinson’s Disease, robustly interacted with each other and triggered endogenous α-synuclein accumulation in a strong manner. However, the detailed pathophysiological process caused by the complex remains to be established.MethodsIn this study, rats were unilaterally inoculated with 15 or 30 μg of this complex or vehicle (phosphate buffered saline, PBS). Over a 6-month period post injection, we then investigated the abundance of pSyn inclusions, nigrostriatal degeneration, and changes in axonal transport proteins to identify the various dynamic pathological changes caused by pSyn aggregates in the nigrostriatal system.ResultsAs expected, rats displayed a dose-dependent increase in the amount of α-synuclein inclusions, and progressive dopaminergic neurodegeneration was observed throughout the study, reaching 30% at 6 months post injection. Impairments in anterograde axonal transport, followed by retrograde transport, were observed prior to neuron death, which was first discovered in the PFFs model.DiscussionThe current results demonstrate the value of a novel rat model of Parkinson’s disease characterized by widespread, “seed”-initiated endogenous α-Syn pathology, impaired axonal transport, and a neurodegenerative cascade in the nigrostriatal system. Notably, the present study is the first to examine alterations in axonal transport proteins in a PFF model, providing an appropriate foundation for future research regarding the mechanisms leading to subsequent neurodegeneration. As this model recapitulates some essential features of Parkinson’s disease, it provides an important platform for further research on specific pathogenic mechanisms and pre-clinical evaluations of novel therapeutic strategies.

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