the same time it may impact vulnerability to LB pathology in PD brains as demonstrated in earlier studies detecting both proteins and mRNA levels (literature overview in Supplementary Table 4). Cell lines or animal models without SNCA showed a synaptic deficit, increased susceptibility to viruses, sensitivity to reward, and resulted in nigrostriatal neurodegeneration underscoring the importance of the presence of α-synuclein for neuronal function. Mutant α-synuclein accelerated cell death induced by various stimuli (staurosporine, serum deprivation, trypsin, or oxidative stress by H2O2), while wild-type α-synuclein exerted anti-apoptotic effects. In contrast to the suggested neuroprotective role of α-synuclein, other studies suggest a deleterious effect when overexpressed and that removing SNCA mediates resistance to LB pathology. Collectively, our findings suggest that low SNCA expression in preclinically involved regions may increase the vulnerability of brain regions to LB pathology.
