Reference Report

Reference
Citation	Lee, F.K., Wong, A.K., Lee, Y.W., Wan, O.W., Chan, H.Y., Chung, K.K. (2009). The role of ubiquitin linkages on alpha-synuclein induced-toxicity in a Drosophila model of Parkinson's disease. J. Neurochem. 110(1): 208--219. (Export to RIS)
FlyBase ID	FBrf0208469
Publication Type	Research paper
PubMed ID	19457126
PubMed Abstract	Parkinson's disease (PD) is a common movement disorder marked by the loss of dopaminergic (DA) neurons in the brain stem and the presence of intraneuronal inclusions designated as Lewy bodies (LB). The cause of neurodegeneration in PD is not clear, but it has been suggested that protein misfolding and aggregation contribute significantly to the development of the disease. Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and autophagy lysosomal pathway (ALP). Recent studies suggested that different types of ubiquitin linkages can modulate these two pathways in the process of protein degradation. In this study, we found that co-expression of ubiquitin can rescue neurons from alpha-syn-induced neurotoxicity in a Drosophila model of PD. This neuroprotection is dependent on the formation of lysine 48 polyubiquitin linkage which is known to target protein degradation via the proteasome. Consistent with our results that we observed in vivo, we found that ubiquitin co-expression in the cell can facilitate cellular protein degradation by the proteasome in a lysine 48 polyubiquitin-dependent manner. Taken together, these results suggest that facilitation of proteasomal protein degradation can be a potential therapeutic approach for PD.
DOI	10.1111/j.1471-4159.2009.06124.x
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Neurochem.
Title	Journal of Neurochemistry
Publication Year	1956-
ISBN/ISSN	0022-3042
Data from Reference
Alleles (10)
	Avic\GFP^{EGFP.Scer\UAS} Hsap\SNCA^Scer\UAS.cFa Hsap\UBC^{K48.Scer\UAS.T:Ivir\HA1} Hsap\UBC^{K48R.Scer\UAS.T:Ivir\HA1} Hsap\UBC^{K63.Scer\UAS.T:Ivir\HA1} Hsap\UBC^{K63R.Scer\UAS.T:Ivir\HA1} Hsap\UBC^{Scer\UAS.T:Ivir\HA1} Scer\GAL4^Ddc.PL Scer\GAL4^elav-C155 Scer\GAL4^GMR.PF
Constructs (9)
	P{Ddc-GAL4.L} P{GAL4-ninaE.GMR} P{UAS-EGFP.L} P{UAS-Hsap\SNCA.F} P{UAS-UBC.HA} P{UAS-UBC.K48} P{UAS-UBC.K48R} P{UAS-UBC.K63} P{UAS-UBC.K63R}
Genes (6)
	Avic\GFP Hsap\SNCA Hsap\UBC Scer\GAL4 T:Ivir\HA1 T:Ivir\haemagglutinin
Insertions (11)
	P{GawB}elav^C155 P{UAS-UBC.HA}2 P{UAS-UBC.HA}6 P{UAS-UBC.K48}2 P{UAS-UBC.K48}6 P{UAS-UBC.K48R}2 P{UAS-UBC.K48R}6 P{UAS-UBC.K63}2 P{UAS-UBC.K63}4 P{UAS-UBC.K63R}2 P{UAS-UBC.K63R}5
Natural transposons (1)
	P-element