In summary, our study showed (i) α-syn overexpression activates autophagy in neurons cells; (ii) nutrient deprivation did not enhance autophagy in cells bearing high level of α-syn; (iii) nutrient deprivation promoted α-syn aggregation and cell apoptosis by triggering ER stress response in which SREBP2 activation and its function on cholesterolgenesis were involved; (iv) these changes were reduced substantially by reducing cholesterolgenesis; and (v) in this regard, down-regulation of SREBP2 activity might be a means to prevent α-syn aggregates accumulation in PD. Here, SREBF2 is linked to Parkinson disease.