Both proteins potently promote cell survival. Thes

Both proteins potently promote cell survival. These proteins are currently the most promising treatment candidates in several neuropathological conditions, but also in diabetes (Voutilainen et al., 2015; Lindholm et al., 2016; Lindahl et al., 2017). Most importantly, MANF and especially CDNF are neurorestorative in the animal models of Parkinson’s disease. Indeed, when applied to the animals with severe chemically induced Parkinsonian symptoms, these factors significantly improve the neurological scores and reduce histological brain damages (Lindholm et al., 2007; Airavaara et al., 2009; Voutilainen et al., 2009, 2011; Huotarinen et al., 2018). MANF is also neurorestorative in the rat model of cerebral stroke (Matlik et al., 2018). The cytoprotective mechanisms of MANF and CDNF are currently poorly understood. Both can protect the cells as intracellular endoplasmic reticulum proteins but at least in the in vivo experiments, also as secreted factors. However, the molecular details for either mode of action are not yet clear