期刊
NEUROBIOLOGY OF DISEASE
卷 97, 期 -, 页码 90-102出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.07.009
关键词
CDNF; MANF; Parkinson's disease; Diabetes; ER stress
资金
- Jane and Aatos Erkko Foundation [4730016]
- Juvenile Diabetes Research Foundation [17-2013-410, 1-INO-2014-162-A-V]
- Michael J. Fox Foundation for Parkinson's Research [7670.01]
- Academy of Finland [268662]
- Academy of Finland (AKA) [268662, 268662] Funding Source: Academy of Finland (AKA)
Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) promote the survival of midbrain dopaminergic neurons which degenerate in Parkinson's disease (PD). However, CDNF and MANF are structurally and functionally clearly distinct from the classical, target-derived neurotrophic factors (NTFs) that are solely secreted proteins. In cells, CDNF and MANF localize in the endoplasmic reticulum (ER) and evidence suggests that MANF, and possibly CDNF, is important for the maintenance of ER homeostasis. MANF expression is particularly high in secretory tissues with extensive protein production and thus a high ER protein folding load. Deletion of MANF in mice results in a diabetic phenotype and the activation of unfolded protein response (UPR) in the pancreatic islets. However, information about the intracellular and extra cellular mechanisms of MANF and CDNF action is still limited. Here we will discuss the structural motifs and physiological functions of CDNF and MANF as well as their therapeutic potential for the treatment of neurodegenerative diseases and diabetes. Currently available knockout models of MANF and CDNF in mice, zebrafish and fruit fly will increase information about the biology of these interesting proteins. (C) 2016 Elsevier Inc. All rights reserved.
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