IGF-1 regulation of oxidative stress in other neurodegenerative disorders (NDs)

ReferenceAuthor (publication year)ND modelIGF-1 modelOxidative stress markersEffects
[67]Li et al., 2017Amyotrophic lateral sclerosis
TDP-25 cells		AAV9-IGF-1Nuclear factor erythroid 2-related factor 2 (Nrf2), as quinone oxidoreductase 1 (NQO1), and the regulatory subunit of glutamate cysteine ligase (GCLM). MitoTracker® Red CM-H2XRosDelivery of AAV9-IGF-1 to TDP25 cells protected mitochondria, such as improved mitochondrial swelling, cristae dilation, and reduced the level of reactive oxygen species (ROS).
[69]Park et al., 2012Prion diseases PrP (106–126) treatment
SH-SY5Y human neuroblastoma cell line		IGF-1 reagentDCFH-DA assay was carried out to ascertain ROS generation
Antioxidant agents (GSH and NAC)		IGF-1 prevents PrP (106–126)-induced ROS generation.
IGF-1 treatment prevents prion-mediated mitochondrial dysfunction and neurotoxicity in neuronal cells.
[71]Calixto et al., 2012C. elegans axonal degeneration
Mice C57BL/6J		Physiological IGF-1 measuresROS analyzed with the fluorogenic probe CellROX Deep Red ReagentInsulin/IGF-1-like signaling is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identifies ROS as a key intermediate of neuronal degeneration in vivo.
[77]Kwak et al., 2012In vitro neurodegeneration induced by zinc (AD, ALS, PD)
Primary cultured cortical neurons		Physiological IGF-1 measuresH2O2 and zincNEDD4-1 is upregulated by a variety of neurotoxins that elicit oxidative stress in neurons, leading to IGF-1R protein degradation via ubiquitin-proteasome system (UPS).
[78]Tarantini et al., 2017Male mice homozygous for a floxed exon 4 of the Igf1 geneIGF-1 deficiencyOxidative stress-mediated MMPIGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and extracellular matrix remodeling, which together with the increased MMP activation likely also contributes to increased fragility of intracerebral arterioles.
[79]Ribeiro et al., 2014Huntington’s disease
Knock-in striatal cells		IGF-1 mediums and serumMitochondrial-driven ROS generationInsulin and IGF-1 treatment further reduced mitochondrial.
ROS production and normalized mitochondrial SOD activity.
[80]Sadagurski et al., 2011R6/2 and R6/2•Irs2ntg mice
Huntington’s disease		Role of insulin/IGF-IRS2 signaling[NAD+]/[NADH] ratio
ATP concentration
ROS concentration in brain extracts was carried out using the cell-permeable dye 2′,7′-dichlorofluorescein diacetate (H2DCFDA)		Increasing Irs2 levels in the brains of R6/2 mice significantly reduced life span and increased neuronal oxidative stress and mitochondrial dysfunction.
[81]Allahdadi et al., 2019Spinal cord injury
SCI contusion model in C57Bl/6 mice		Bone marrow-derived mesenchymal stem cells, overexpressing IGF-1NOS2 (type I activation marker, Inos), nitrite concentrationNitrite concentration was significantly reduced in the BMMSC-IGF-1-treated group when compared to saline.
[82]Gustafsson et al., 2004Diabetic neurite degeneration induced by hyperglycemia SH-SY5Y cellsHuman recombinant IGF-1 in insulin-free N2 mediumUCP3 protein expression
MMP, intracellular levels of ROS, and total glutathione		IGF-1 prevented a decline in UCP3 protein expression following glucose treatment. Simultaneously, glucose-induced increases in MMP and mitochondrial ROS production and reduction in the number of neurites per cell were abolished or significantly reduced.