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.
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: avik_roy@rush.edu.
Avik
A
Roy
Kalipada
K
Pahan
D000818:Animals; D017089:Ankyrin Repeat; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D010300:Parkinson Disease / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000378:metabolism*
C585874:Abtb2 protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051844:alpha-Synuclein
ABTB2; BPOZ-2; Neuron; α-Synuclein