Mesencephalic astrocyte-derived neurotrophic factor (MANF) has a unique mechanism to rescue apoptotic neurons |
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| Authors: | Hellman Maarit Arumäe Urmas Yu Li-ying Lindholm Päivi Peränen Johan Saarma Mart Permi Perttu |
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| Institution: | Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland. |
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| 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. |
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| Keywords: | Apoptosis Neurodegeneration Neurotrophic Factor NMR Parkinson Disease Bax Ku70 |
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