Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Nuclear / genetics
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Antigens, Nuclear / metabolism
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Apoptosis*
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Disease Models, Animal
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Humans
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Ku Autoantigen
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism*
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Neurons / metabolism*
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Nuclear Magnetic Resonance, Biomolecular
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Oxidopamine / adverse effects
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Oxidopamine / pharmacology
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Parkinson Disease, Secondary / chemically induced
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Parkinson Disease, Secondary / genetics
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Parkinson Disease, Secondary / metabolism*
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / metabolism*
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Rats
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Structural Homology, Protein
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Sympatholytics / adverse effects
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Sympatholytics / pharmacokinetics
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Antigens, Nuclear
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BAX protein, human
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Bax protein, rat
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DNA-Binding Proteins
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MANF protein, human
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MANF protein, rat
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Nerve Growth Factors
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Proteins
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Sympatholytics
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bcl-2-Associated X Protein
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Oxidopamine
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Xrcc6 protein, human
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Xrcc6 protein, rat
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Ku Autoantigen