Open AccessHistone Decacetylase Inhibitors Prevent Mitochondrial Fragmentation and Elicit Early Neuroprotection against MPP +
Author(s) -
Zhu Min,
Li WenWei,
Lu ChuanZhen
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12217
Subject(s) - histone deacetylase , mfn2 , programmed cell death , neuroprotection , microbiology and biotechnology , trichostatin a , biology , histone deacetylase inhibitor , fragmentation (computing) , mitochondrion , neurodegeneration , rotenone , apoptosis , chemistry , mitochondrial fusion , histone , pharmacology , biochemistry , mitochondrial dna , medicine , pathology , disease , ecology , gene
Summary Background Parkinson's disease ( PD ) is a common neurodegenerative disease, characterized by progressive loss of dopaminergic ( DA ) neurons in the substantia nigra. Recent investigations have shown that mitochondrial fragmentation, an early event during apoptosis, is implicated in the degeneration of DA neurons in PD , and more importantly, preventing mitochondrial fragmentation could rescue cell death in several PD models. Therefore, mitochondrial dynamics may be a therapeutic target for early intervention in PD . However, much remains unknown about the mechanism underlying mitochondrial fragmentation in PD . Methods The alterations in mitochondrial morphology, cell apoptosis, and mitochondrial shaping protein levels were detected after SH ‐ SY 5Y cells were treated with various doses of MPP + or rotenone. Results Mitochondrial fragmentation is an early event during apoptosis caused by MPP + but not rotenone, and Trichostatin A ( TSA ), a commonly used histone deacetylase ( HDAC ) inhibitor, selectively rescues mitochondrial fragmentation and cell death induced by lower doses of MPP +. Mitochondrial fragmentation triggered by lower doses of MPP + may be a result of Mfn2 down‐regulation, which could be completely reversed by TSA . Further investigation suggests that TSA prevents MPP +‐induced Mfn2 down‐regulation via inhibiting histone deacetylation over Mfn2 promoter and alleviating its transcriptional dysfunction. Conclusions Histone deacetylase inhibitors prevent mitochondrial fragmentation and elicit early neuroprotection in PD cell model induced by MPP +. Hence, HDAC inhibitors may be a potential early treatment for PD .