Mesencephalic astrocyte-derived neurotrophic factor (MANF) has a unique mechanism to rescue apoptotic neurons.

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.

• Authors: Maarit Hellman, Urmas Arumäe, Li-ying Yu, Päivi Lindholm, Johan Peränen, Mart Saarma, Perttu Permi
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 4 Pg. 2675-80 (Jan 28 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21047780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Nuclear
• BAX protein, human
• Bax protein, rat
• DNA-Binding Proteins
• MANF protein, human
• MANF protein, rat
• Nerve Growth Factors
• Proteins
• Sympatholytics
• bcl-2-Associated X Protein
• Oxidopamine
• Xrcc6 protein, human
• Xrcc6 protein, rat
• Ku Autoantigen

Topics

• Animals
• Antigens, Nuclear (genetics, metabolism)
• Apoptosis
• Cells, Cultured
• DNA-Binding Proteins (genetics, metabolism)
• Disease Models, Animal
• Humans
• Ku Autoantigen
• Nerve Growth Factors (genetics, metabolism)
• Neurons (metabolism)
• Nuclear Magnetic Resonance, Biomolecular
• Oxidopamine (adverse effects, pharmacology)
• Parkinson Disease, Secondary (chemically induced, genetics, metabolism)
• Protein Structure, Tertiary
• Proteins (genetics, metabolism)
• Rats
• Structural Homology, Protein
• Sympatholytics (adverse effects, pharmacokinetics)
• bcl-2-Associated X Protein (genetics, metabolism)