1H, 13C and 15N resonance assignments of the human mesencephalic astrocyte-derived neurotrophic factor

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease, where dopaminergic cells die most prominently in the area of substantia nigra. Neurotrophic factors (NTFs) are secreted proteins, which upon binding to their target receptors trigger survival pathways to prevent neuronal loss. Recently discovered NTFs mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF) most efficiently protect and repair the dopaminergic neurons in the animal 6-OHDA models of PD. However, the neuroprotective mechanism of MANF/CDNF is currently elusive. To this end, we have employed high-resolution NMR spectroscopy to determine three-dimensional structure of full-length human MANF in solution and characterized C-terminal domain as structural unit of MANF protein.