The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF-2-associated pathways and thereby enhancing their protective effects against AD.
Genome-wide RNA sequencing analysis reveals that IGF-2 attenuates memory decline, oxidative stress and amyloid plaques in an Alzheimer's disease mouse model (AD) by activating the PI3K/AKT/CREB signaling pathway.
Notwithstanding these results, additional studies are required to validate and fully characterize the function of the IGF-II/M6P receptor in the normal brain and its involvement in various neurodegenerative disorders including AD.
The results suggest that: 1) IGF-I, IGF-II, and neurotrophin signaling are more impaired in DLB than PD, corresponding with DLB's more pronounced neurodegeneration, oxidative stress, and alpha-synuclein accumulation; 2) MnCl2 exposure causes PD/DLB associated abnormalities in central nervous system neurons, and therefore may contribute to their molecular pathogenesis; and 3) molecular abnormalities in PD/DLB overlap with but are distinguishable from Alzheimer's disease.
Realtime quantitative RT-PCR analysis of frontal lobe tissue demonstrated that increasing AD Braak Stage was associated with progressively reduced levels of mRNA corresponding to insulin, IGF-I, and IGF-II polypeptides and their receptors, tau, which is regulated by insulin and IGF-I, and the Hu D neuronal RNA binding protein.
Since alterations in the expression of INS or IGF-2 might be relevant in AD, we investigated the association between the INS VNTR polymorphism and the risk for AD.