Premium
Effects of Inducible Expression of Alpha‐Synuclein on Proteasome and Mitochondria in a Neuroblastoma Cell Line
Author(s) -
Nahreini Piruz,
Andreatta Cynthia,
Prasad Kedar N,
Toribara Neil W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb79
Subject(s) - proteasome , microbiology and biotechnology , cell culture , intracellular , alpha synuclein , mitochondrion , biology , programmed cell death , neurodegeneration , neuroblastoma , cell , sh sy5y , oxidative stress , chemistry , parkinson's disease , apoptosis , biochemistry , genetics , medicine , disease , pathology
Aggregation of human alpha‐synuclein (a‐SYN) is associated with the pathogenesis of some neurodegenerative disorders, notably Parkinson's disease (PD). Increased expression or mutations of a‐SYN promote protein aggregation, which presumably mediates neuronal cell toxicity. We hypothesize that aggregated a‐SYN inhibits proteasome activity and/or interferes with mitochondrial membrane potential (MMP), resulting in neuronal cell death. We used a murine neuroblastoma cell line (NBP2), which terminally differentiates into mature neurons in response to an increase in the intracellular levels of cAMP. To elucidate the mechanism of a‐SYN mediated cell toxicity, we established a stable doxycycline‐regulated expression (TetOff) of human a‐SYN in NBP2 cells. Additionally, we developed a NBP2 cell line that constitutively overexpresses a‐SYN. Our data suggest that overexpression of a‐SYN may interfere with proteasome activity as well as enhance cell sensitivity to oxidative stress. Our ongoing work will reveal the mechanism(s) through which a‐SYN mediates its toxicity in differentiated NBP2 cells.