α-Synuclein Aggregation in Cholinergic Neurons: A Novel Cell Model and Its Implications for Parkinson's Disease understanding

Abstract

This study aimed to explore the aggregation of α-synuclein within cholinergic neurons and its implications for Parkinson's disease (PD) pathogenesis. Novel cell model for cholinergic cells was developed by using differentiated LAN-2 neuroblastoma cells treated with human α-SYN aggregates. Cellular toxicity, mitochondrial dysfunction, and neuroinflammation-those features critical for neurodegeneration-developed as a result of the uptake of α-SYN aggregates by cholinergic neurons. The current finding thus supported the prion-like transmission of α-SYN and its role in spreading neurodegeneration throughout the brain. However, this study also suggests addressing α-SYN phosphorylation and aggregation as an important component of therapeutic approaches designed to alleviate motor and non-motor symptoms in PD. Our work hereby provides a new tool for basic research in cholinergic neuron degeneration and the preclinical evaluation of therapeutic strategies targeting α-SYN pathology. This work underlines the unmet need for novel therapeutic strategies for the cholinergic system in PD.