IGF-1 regulation of oxidative stress in Alzheimer’s disease (AD) and related dementias

ReferenceAuthor (publication year)AD modelIGF-1 modelOxidative stress markersEffects of IGF-1
[33]Selles et al., 2020Primary hippocampal neuronal cultures.
16–19-month-old transgenic APPswe/PS1ΔE9 (APP/PS1) mice 3-month-old Swiss mice that received a single intracerebroventricular infusion of amyloid-β oligomers (AβOs).		Recombinant adenoviral vector, RAd-IGF-1Various types of (reactive oxygen species) ROS formation, including hydrogen peroxide, hydroxyl radical, peroxyl radicals, and peroxynitriteIGF-1/IGF-1R pathway is affected in the AD hippocampus as well as in the hippocampus of mouse models of AD.
Adenoviral-mediated expression of IGF1 protects hippocampal neurons from AβO toxicity and prevents memory impairment induced by AβOs in mice.
[41]Liu et al., 2020Adult male Sprague–Dawley rats, intracerebroventricular injections of streptozotocin (STZ)Physiological IGF-1 measuresSilibinin significantly decreased STZ-induced tau hyperphosphorylation (ser404) in hippocampus and cerebral cortex, markedly inhibited apoptosis of neurons induced by STZSilibinin increased the expression of insulin receptor and IGF-1R protein in the hippocampus.
[12]Logan et al., 2018Mice GFAP-CreERT2/Igfrf/f
Young and old C57Bl/6
Astrocyte primary cultures		Reduction in circulating levels of IGF-1Mitochondrial electron transport chain function and oxidative phosphorylation mitochondrial respiration, ROS generation, and OXPHOS coupling efficiencyIGFR deficient astrocytes also displayed altered mitochondrial structure and function and increased mitochondrial ROS production associated with the induction of an antioxidant response.
[42]Liou et al., 2019Human brain tissue
Postmortem frontal (Brodmann’s area [BA]8/9 and BA24) and temporal (BA38) lobe homogenates		Physiological IGF-1 measuresHNEThe brains with FTLD had significantly elevated mean levels of pTau, ubiquitin, TGF-b1, and HNE, reflecting known neuropathologic processes including aberrantly increased Tau phosphorylation, protein ubiquitination, and neuroinflammation.
Oxidative stress with lipid peroxidation product accumulations, which overlap with altered expression of insulin/IGF signaling ligands and receptors.
IGF-1 was increased in BA24, and IGF-1R was upregulated in all three brain regions.
[43]Kuang et al., 2014Male 10-month-old SAMP8 and SAMR1 mice
293T cells		Physiological IGF-1R measuresThe lipid peroxidation product MDA, carbonylated proteins, and the DNA oxidation product 8-hydroxy-desoxyguanosineLigustilide induced the IGF-1 signaling inhibition and FoxO1 activation through Klotho upregulation.
Klotho might alleviate oxidative stress by activating FoxO transcription factors that are negatively regulated by the insulin/IGF-1 signaling pathway, inducing the transcription of antioxidative enzymes, such as manganese superoxide dismutase and catalase, and removing ROS.
[44]Cheng et al., 2005Transgenic miceIGF-I gene-targeted mice (Igf1−/−)Deposition of NT residues and enzymes involved in the production of nitric oxide, nitric oxide synthetases (NOS)IGF-I regulates tau phosphorylation in the aging brain.