Role of alpha-synuclein in Parkinson's disease progression from a neurovascular perspective

초록

Abnormal misfolding of α-synuclein in the brain leads to cellular dysfunction in specific neuronal populations, ultimately resulting in neuronal death and the progression of Parkinson’s disease (PD). In addition to its well-established pathological role in the nervous system, a growing body of evidence suggests that vascular impairment is also associated with the early stages of PD pathogenesis. However, the precise role of α-synuclein in neurovascular dysfunction remains poorly understood. In this study, we investigated neurovascular impairments in a familial mutant PD mouse model. We found that young PD mice exhibited impaired vascular network development, likely driven by abnormal neural activity. To further explore peripheral contributions to vascular pathology, we developed a novel mouse model in which human α-synuclein is secreted into the extracellular space. Interestingly, despite sustained exposure to elevated α-synuclein levels in the blood plasma, cerebrovascular damage was minimal. These findings suggest that the pathological impact of α-synuclein on the vascular system may vary depending on its origin, highlighting the complexity of its role in PD progression.