ARTICLE 1 H, 13 C and 15 N resonance assignments of the human mesencephalic astrocyte-derived neurotrophic factor Maarit Hellman • Johan Pera ¨nen • Mart Saarma • Perttu Permi Received: 11 May 2010 / Accepted: 29 June 2010 / Published online: 9 July 2010 Ó Springer Science+Business Media B.V. 2010 Abstract Parkinson’s disease (PD) is a chronic, progres- sive neurodegenerative disease, where dopaminergic cells die most prominently in the area of substantia nigra. Neu- rotrophic factors (NTFs) are secreted proteins, which upon binding to their target receptors trigger survival pathways to prevent neuronal loss. Recently discovered NTFs mesen- cephalic 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 neuro- protective 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. Keywords Apoptosis Á Neurotrophic factors Á Parkinson’s disease Á NMR assignments Biological context Programmed neuronal death, apoptosis, is a key process in the development of neuronal population. Indeed, initial overproduction of neurons is counterbalanced by apoptosis to limit the number of neurons to match actual requirement of a particular tissue. Programmed neuronal death is neu- tralized by the intervention of neurotrophic factors targeted to rescue apoptotic neurons from death. Hence, neuron population is regulated by neurotrophic factors to meet requirements of a given tissue. Neurotrophic factors include three protein families, the neurotrophins (NGF, BDNF, NT3, NT4/5/6/7), the neurokines (CNTF, IL-6, LIF) and glial cell line-derived neurotrophic factors GDNF, NRTN, PSPN and ARTN). Neurotrophic factors are secreted proteins, which upon binding to their target receptor trigger survival pathways (reviewed by Butte 2001). Parkinson’s disease (PD) is a chronic, progressive neu- rodegenerative disease, where dopaminergic cells die most prominently in the area of substantia nigra. Neuronal loss leads to motor symptoms e.g. muscle rigidity, tremor, and a slowing of physical movement. Several treatments for PD have been utilized, but none of them seems to arrest the progression of the cell death. The most potent treatment of neurotrophic factors for dopaminergic neurons is GDNF. GDNF family ligands associate to specific GFRa receptors and active receptor tyrosine kinase (RET). Regrettably, recent data show low benefits with severe side effects of GDNF treatment. Recently discovered proteins mesencephalic astrocyte- derived neurotrophic factor (MANF) (Petrova et al. 2003) and its vertebrate paralogue, cerebral dopamine neuro- throphic factor (CDNF) (Lindholm et al. 2007) are prom- ising targets for the treatment of neurodegenerative diseases e.g., PD. MANF and CDNF are secreted proteins, which contain eight highly conserved cysteine residues. They are able to promote the survival of dopaminergic neurons in a 6-hydroxydopamine based experimental model of PD with the efficiency comparable to GDNF. M. Hellman (&) Á P. Permi (&) Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, P.O. Box 65, 00014 Helsinki, Finland e-mail: Maarit.Hellman@helsinki.fi P. Permi e-mail: Perttu.Permi@helsinki.fi J. Pera ¨nen Á M. Saarma Cellular Biotechnology, Institute of Biotechnology, University of Helsinki, P.O. Box 65, 00014 Helsinki, Finland 123 Biomol NMR Assign (2010) 4:215–217 DOI 10.1007/s12104-010-9251-8