TY - JOUR
T1 - α-synuclein protects naive but not dbcAMP-treated dopaminergic cell types from 1-methyl-4-phenylpyridinium toxicity
AU - Jensen, Penny J.
AU - Alter, Benedict J.
AU - O'Malley, Karen L.
PY - 2003/7
Y1 - 2003/7
N2 - The pre-synaptic protein, α-synuclein, has been associated with the pathogenesis of Parkinson's disease. The present study indicates that α-synuclein, but not its mutants (A53T, A30P), can protect CNS dopaminergic cells from the parkinsonism-inducing drug 1-methyl-4-phenylpyridinium (MPP+), whereas it cannot protect from the dopaminergic toxin, 6-hydroxydopamine, hydrogen-peroxide, or the β-amyloid peptide, A-β. Protection from MPP+ was directly correlated with the preservation of mitochondrial function. Specifically, α-synuclein rescued cells from MPP+ mediated decreases in mitochondrial dehydrogenase activity and loss of ATP levels by utilizing ketosis. It also prevented toxin-induced activation of the creatine kinase/creatine phosphate system. Similarly, α-synuclein protected cells from the complex I inhibitor rotenone and 3-nitroproprionic acid, a complex II inhibitor. Wild-type α-synuclein-mediated neuroprotection and subsequent alterations in energy were not found in dbcAMP-differentiated cells. These results suggest that the normal physiological role for α-synuclein may change during development.
AB - The pre-synaptic protein, α-synuclein, has been associated with the pathogenesis of Parkinson's disease. The present study indicates that α-synuclein, but not its mutants (A53T, A30P), can protect CNS dopaminergic cells from the parkinsonism-inducing drug 1-methyl-4-phenylpyridinium (MPP+), whereas it cannot protect from the dopaminergic toxin, 6-hydroxydopamine, hydrogen-peroxide, or the β-amyloid peptide, A-β. Protection from MPP+ was directly correlated with the preservation of mitochondrial function. Specifically, α-synuclein rescued cells from MPP+ mediated decreases in mitochondrial dehydrogenase activity and loss of ATP levels by utilizing ketosis. It also prevented toxin-induced activation of the creatine kinase/creatine phosphate system. Similarly, α-synuclein protected cells from the complex I inhibitor rotenone and 3-nitroproprionic acid, a complex II inhibitor. Wild-type α-synuclein-mediated neuroprotection and subsequent alterations in energy were not found in dbcAMP-differentiated cells. These results suggest that the normal physiological role for α-synuclein may change during development.
KW - Cell death
KW - Differentiation
KW - MPP
KW - Parkinson's disease
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=0037971160&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2003.01835.x
DO - 10.1046/j.1471-4159.2003.01835.x
M3 - Article
C2 - 12807439
AN - SCOPUS:0037971160
VL - 86
SP - 196
EP - 209
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 1
ER -