Intracranially (extracellularly) injected MANF effectively protected dopaminergic neurons in a rat model of 6-hydroxydopamine induced Parkinson’s disease (Voutilainen et al., 2009) and the ischemia model (Mikko et al., 2009), thereby suggesting it to function as a secreted neurotrophic factor (Lindholm et al., 2007; Mikko et al., 2009; Voutilainen et al., 2009). This evidence concerns the gene MANF and ischemia.