Accordingly, AKT activity appears to be involved in IGF-1 neuroprotection in experimental PD (453), and activity of this kinase in PD links PINK1, which is mutated in familial PD cases, with IGF-1R (107), while PD brains show increased levels of Ser-phosphorylated IRS-1, a marker of IGF-1R/IR insensitivity (454). Here, IRS1 is linked to Parkinson disease.