Ankyrin repeat and BTB/POZ domain containing protein-2 inhibits the aggregation of alpha-synuclein: Implications for Parkinson's disease

Aggregation of α-synuclein is a pathological hallmark of sporadic or familial PD. However, the detailed molecular mechanism responsible for the aggregation of α-synuclein has not been properly explored. In the present study, we have identified a novel role of an anti-tumorigenic BTB/POZ domain containing protein-2 (BPOZ-2) in the regulation of α-synuclein accumulation in dopaminergic (DA) neurons. MPP+, an etiological factor for PD, significantly downregulated the expression of BPOZ-2 ahead of α-synuclein upregulation. Moreover, siRNA knockdown of BPOZ-2 alone stimulated the aggregation of α-synuclein protein; the effect was further induced in presence of MPP+ in mouse primary DA neurons. Finally, the absence of BPOZ-2 in α-synuclein expressing neuronal populations of MPTP-intoxicated mouse and primate nigra indicates that the suppression of BPOZ-2 could be involved in the accumulation of α-synuclein protein.