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Attenuation of MPTP‐induced neurotoxicity and locomotor dysfunction in Nucling‐deficient mice via suppression of the apoptosome pathway
Author(s) -
Teng Xichuan,
Sakai Takashi,
Liu Li,
Sakai Rika,
Kaji Ryuji,
Fukui Kiyoshi
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03833.x
Subject(s) - mptp , neurotoxicity , neurotoxin , substantia nigra , neurodegeneration , apoptosome , dopaminergic , apoptosis , biology , pharmacology , caspase , neuroscience , programmed cell death , endocrinology , medicine , biochemistry , dopamine , toxicity , disease
1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced neurotoxicity is one of the experimental models most commonly used to study the pathogenesis of Parkinson's disease (PD). Although the biochemical mechanisms underlying the cell death induced by MPTP remain to be clarified, it has been found that the mitochondrial apoptotic signaling pathway plays an important role in the neurotoxicity of MPTP. Nucling is a novel type of apoptosis‐associated molecule, essential for cytochrome c , apoptosis protease activating factor 1 (Apaf‐1), pro‐caspase‐9 apoptosome induction and caspase‐9 activation following pro‐apoptotic stress. Here we found that Nucling‐deficient mice treated with MPTP did not exhibit locomotor dysfunction in an open‐field test. The substantia nigra dopaminergic neurons of Nucling‐deficient mice were resistant to the damaging effects of the neurotoxin MPTP. Up‐regulated expression of apoptosome was attenuated in Nucling‐deficient mice treated with MPTP. These results indicate an important role for Nucling in MPTP‐induced neuronal degeneration and suggest that the suppression of Nucling would be of therapeutic benefit for the treatment of neurodegeneration in PD.