Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.yexcr.2005.10.012
Title: Dopamine-related and caspase-independent apoptosis in dopaminergic neurons induced by overexpression of human wild type or mutant α-synuclein
Authors: Zhou, Z.D. 
Yap, B.P.
Gung, A.Y.T.
Leong, S.M. 
Ang, S.T.
Lim, T.M. 
Keywords: α-synuclein
Apoptosis
Caspase
Dopamine
Doxycycline
Neurotoxins
Parkinson's disease
Issue Date: 15-Jan-2006
Citation: Zhou, Z.D., Yap, B.P., Gung, A.Y.T., Leong, S.M., Ang, S.T., Lim, T.M. (2006-01-15). Dopamine-related and caspase-independent apoptosis in dopaminergic neurons induced by overexpression of human wild type or mutant α-synuclein. Experimental Cell Research 312 (2) : 156-170. ScholarBank@NUS Repository. https://doi.org/10.1016/j.yexcr.2005.10.012
Abstract: Human wild type (WT) and mutant α-synuclein (α-syn) genes were overexpressed using a Tet-on expression system in stably transfected dopaminergic MN9D cells. Their overexpression induced caspase-independent and dopamine-related apoptosis not rescued by general caspase inhibitor Z-VAD-FMK. While apoptosis due to overexpression of WT α-syn was completely abrogated by a specific tyrosine hydroxylase (TH) inhibitor, α-methyl-p-tyrosine (α-MT), the inhibitor only partially rescued apoptosis caused by overexpression of α-syn mutants. In addition, overexpression of mutants enhanced the toxicity of 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxyldopamine (6-OHDA) to MN9D cells, whereas overexpression of WT protected MN9D cells against MPP+ toxicity, but not against 6-OHDA. We conclude that WT α-syn is beneficial to dopaminergic neurons but its overexpression in the presence of endogenous dopamine makes it a potential threat to the cells. In contrast, mutant α-syn not only caused the loss of WT protective function but also the gain-of-toxicity which becomes more serious in the presence of dopamine and neurotoxins. © 2005 Elsevier Inc. All rights reserved.
Source Title: Experimental Cell Research
URI: http://scholarbank.nus.edu.sg/handle/10635/100502
ISSN: 00144827
DOI: 10.1016/j.yexcr.2005.10.012
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