Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease

Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons

“…Our results indicated that IGF-II protects the neurons against ROS production and the dramatic increase in the levels of the cell damage markers AOPP and LOOH; the reduction in TAS and GPX activity is also counteracted. These changes agree with previous results in cellular models of PD [ 24 , 27 ] and after administration of CORT in neuronal cultures [ 12 ], where IGF-II prevented oxidative balance and GPX expression.…”

“…Parkinson disease and conditions of emotional stress are strongly related to increases in oxidative distress and mitochondrial damage, contributing to enlarged neurodegeneration and/or death [ 18 , 39 , 51 , 52 , 53 ]. The protective effect of IGF-II found in the cellular oxidative stress model induced by the CORT [ 12 , 13 ] and the PD models [ 24 , 27 ], which is mediated through its specific IGF-IIR, suggests a potential decrease in the mitochondrial-oxidative damage observed in this combined PD experimental model after IGF-II administration, leading to protecting dopaminergic neurons from cell death. Accordingly, the co-incubation with IGF-II and both drugs prevented the release of LDH, whereas the incubation in the presence of an inhibitor of IGF-IR and RIns (BMS) used to define the receptor involved in the IGF-II effect, did not modify the effect of IGF-II.…”

“…For mitochondrial O 2 consumption and immunocytochemistry, wells were pre-coated with 100 μg/mL of poly- d -lysine. Cells were treated with 200 μM MPP + , 0.5 μM CORT [ 17 ] (Merck/MilliporeSigma, Burlington, MA, USA), and 25 ng/mL IGF-II (provided by Lilly Laboratories, Madrid, Spain) for 2.5 or 6 h [ 17 , 24 ]. The treatments were applied in a modified Locke’s solution (137 mM NaCl, 5 mM CaCl 2 , 10 mM KCl, 25 mM glucose, 10 mM Hepes, pH: 7.4) supplemented with 1% penicillin/streptomycin and 2 mM l -glutamine.…”

“…Although the specific functions of IGF-II are still poorly understood in adults, new evidence is emerging on the role of IGF-II as a key neuroprotective factor in pathological conditions, the study of IGF-II in neurodegenerative diseases being of increasing interest [ 21 , 22 , 23 ]. To date, only a small number of studies relate the neuroprotective mechanisms of IGF-II to its antioxidant function [ 12 , 13 , 23 , 24 , 25 , 26 , 27 , 28 ]. Thus, IGF-II has been shown to exhibit neuroprotective actions in Alzheimer’s disease, PD and ageing conditions [ 24 , 25 , 28 ], glucocorticoid-mediated stress situations [ 12 , 13 ], and neuropsychiatric disorders such as schizophrenia and autism [ 29 , 30 , 31 ].…”

“…To date, only a small number of studies relate the neuroprotective mechanisms of IGF-II to its antioxidant function [ 12 , 13 , 23 , 24 , 25 , 26 , 27 , 28 ]. Thus, IGF-II has been shown to exhibit neuroprotective actions in Alzheimer’s disease, PD and ageing conditions [ 24 , 25 , 28 ], glucocorticoid-mediated stress situations [ 12 , 13 ], and neuropsychiatric disorders such as schizophrenia and autism [ 29 , 30 , 31 ].…”