Neuroprotection of Parkin against apoptosis is independent of inclusion body formation.
Loss-of-function mutations in the parkin gene are known to result in autosomal recessive juvenile parkinsonism, which causes selective degeneration of nigrostriatal dopaminergic neurons in the absence of Lewy bodies. Here, we show that overexpression of parkin protects PC12 cells from neurotoxin of the proteasome inhibitor lactacystin and increases the accumulation of ubiquitin-protein conjugates and the formation of ubiquitin-positive inclusions induced by lactacystin. However, the protective effect of parkin against lactacystin-induced apoptosis is not associated with its ability to promote the formation of ubiquitinated inclusions. It is likely that Lewy body formation may be only a compensatory mechanism of dopaminergic neurons attempting to counteract toxicity, and not the ultimate cause of neuronal death.
Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025,China.
Hui
H
Yang
Hai-Yan
HY
Zhou
Biao
B
Li
Sheng-Di
SD
Chen
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D025801:Ubiquitin / Q000096:biosynthesis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein