Reference Report

Reference
Citation	Yang, Y., Nishimura, I., Imai, Y., Takahashi, R., Lu, B. (2003). Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37(6): 911--924. (Export to RIS)
FlyBase ID	FBrf0159258
Publication Type	Research paper
PubMed ID	12670421
PubMed Abstract	Parkin, an E3 ubiquitin ligase that degrades proteins with aberrant conformations, is associated with autosomal recessive juvenile Parkinsonism (AR-JP). The molecular basis of selective neuronal death in AR-JP is unknown. Here we show in an organismal system that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic (DA) neurons. Coexpression of Parkin degrades Pael-R and suppresses its toxicity, whereas interfering with endogenous Drosophila Parkin function promotes Pael-R accumulation and augments its toxicity. Furthermore, overexpression of Parkin can mitigate alpha-Synuclein-induced neuritic pathology and suppress its toxicity. Our study implicates Parkin as a central player in the molecular pathway of Parkinson's disease (PD) and suggests that manipulating Parkin expression may provide a novel avenue of PD therapy.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Neuron
Title	Neuron
Publication Year	1988-
ISBN/ISSN	0896-6273
Data from Reference
Alleles (15)
	Hsap\GPR37^Scer\UAS.cYa Hsap\PARK2^Scer\UAS.cYa Hsap\SNCA^{A30P.Scer\UAS} Hsap\SNCA^{A53T.Scer\UAS} Hsap\SNCA^Scer\UAS.cFa park^{dsRNA.Scer\UAS} Scer\GAL4^ap-md544 Scer\GAL4^Ddc.PL Scer\GAL4^dpp.blk1 Scer\GAL4^elav-C155 Scer\GAL4^ey.PH Scer\GAL4^GMR.PF Scer\GAL4^how-24B Scer\GAL4^hs.PB w^+mC
Constructs (9)
	P{Ddc-GAL4.L} P{GAL4-dpp.blk1} P{GAL4-Hsp70.PB} P{UAS-hParkin.Y} P{UAS-Hsap\SNCA.A30P} P{UAS-Hsap\SNCA.A53T} P{UAS-Hsap\SNCA.F} P{UAS-Pael-R.Y} P{UAS-park.IR}
Genes (11)
	Cha Ddc futsch Hsap\GPR37 Hsap\PARK2 Hsap\SNCA numb park ple Scer\GAL4 w
Insertions (3)
	P{GawB}ap^md544 P{GawB}elav^C155 P{GawB}how^24B