title: Lack of direct role of parkin in the steady-state level and aggregation of alpha-synuclein and the clearance of pre-formed aggregates.
abstract: Mutations in parkin and alpha-synuclein (alpha-syn) are linked to heritable forms of Parkinson's disease (PD). Recently, it has been shown that parkin mitigates alpha-syn-induced neuronal cell death in animal and tissue culture models, suggesting that there is a functional relationship between these two proteins. Although the mechanism by which parkin protects cells from alpha-syn-induced cytotoxicity remains elusive, it is tempting to speculate that parkin might directly regulate the normal metabolism and aggregation of alpha-syn. In the current study, we show that neither the suppression of endogenous parkin expression nor ectopic overexpression affects the steady-state levels of endogenous alpha-syn expression, overall aggregation of this protein, or breakdown of pre-formed aggregates in human neuroblastoma cells. These results suggest that parkin is not directly involved in the metabolism of alpha-syn, its aggregation, or the clearance of pre-formed aggregates.
authors.affiliation: The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089, USA.
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Smita
authors.initials: S
authors.lastname: Patel
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009447:Neuroblastoma; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D034741:RNA, Small Interfering; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde