Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are a novel evolutionary conserved neurotrophic factor (NTF) family. There are two distinct domains in MANF and CDNF 3-dimentional structure, N-terminal saposin-like domain and C-terminal SAP-domain, which suggest their unique mode of action. Although identified for their neurotrophic activity, recent studies have shown MANF and CDNF can protect cells during endoplasmic reticulum (ER) stress. This review summarizes the unique structure and related potential protective role for cells during ER stress of MANF and CDNF.
