{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sohrabi M"],"funding":["NIA NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["200"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7348663"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14"],"pubmed_abstract":["Aging is a major risk factor for Alzheimer's disease (AD). Insulin-like growth factor-1 receptor (IGF-1R) regulates general aging and lifespan. However, the contribution of IGF-1 to age-related AD pathology and progression is highly controversial. Based on our previous work, AβPP/PS1 double transgenic mice, which express human mutant amyloid precursor protein (APP) and presenilin-1 (PS-1), demonstrated a decrease in brain IGF-1 levels when they were crossed with IGF-1 deficient Ames dwarf mice (df/df). Subsequently, a reduction in gliosis, amyloid-β (Aβ) plaque deposition, and Aβ<sub>1-40/42</sub> concentrations were observed in this mouse model. This supported the hypothesis that IGF-1 may contribute to the progression of the disease. To assess the role of IGF-1 in AD, 9-10-month-old male littermate control wild type and AβPP/PS1 mice were randomly divided into two treatment groups including control vehicle (DMSO) and picropodophyllin (PPP), a selective, competitive, and reversible IGF-1R inhibitor. The brain penetrant inhibitor was given ip. at 1 mg/kg/day. Mice were sacrificed after 7 days of daily injection and the brains, spleens, and livers were collected to quantify histologic and biochemical changes. The PPP-treated AβPP/PS1 mice demonstrated attenuated insoluble Aβ<sub>1-40/42</sub>. Additionally, an attenuation in microgliosis and protein p-tyrosine levels was observed due to drug treatment in the hippocampus. Our data suggest IGF-1R signaling is associated with disease progression in this mouse model. More importantly, modulation of the brain IGF-1R signaling pathway, even at mid-life, was enough to attenuate aspects of the disease phenotype. This suggests that small molecule therapy targeting the IGF-1R pathway may be viable for late-stage disease treatment."],"journal":["Frontiers in cellular neuroscience"],"pubmed_title":["IGF-1R Inhibitor Ameliorates Neuroinflammation in an Alzheimer's Disease Transgenic Mouse Model."],"pmcid":["PMC7348663"],"funding_grant_id":["U54 GM128729","P20 GM103442","R01 AG048993","P20 GM113123","R01 AG042819"],"pubmed_authors":["Floden AM","Sohrabi M","Manocha GD","Klug MG","Combs CK"],"additional_accession":[]},"is_claimable":false,"name":"IGF-1R Inhibitor Ameliorates Neuroinflammation in an Alzheimer's Disease Transgenic Mouse Model.","description":"Aging is a major risk factor for Alzheimer's disease (AD). Insulin-like growth factor-1 receptor (IGF-1R) regulates general aging and lifespan. However, the contribution of IGF-1 to age-related AD pathology and progression is highly controversial. Based on our previous work, AβPP/PS1 double transgenic mice, which express human mutant amyloid precursor protein (APP) and presenilin-1 (PS-1), demonstrated a decrease in brain IGF-1 levels when they were crossed with IGF-1 deficient Ames dwarf mice (df/df). Subsequently, a reduction in gliosis, amyloid-β (Aβ) plaque deposition, and Aβ<sub>1-40/42</sub> concentrations were observed in this mouse model. This supported the hypothesis that IGF-1 may contribute to the progression of the disease. To assess the role of IGF-1 in AD, 9-10-month-old male littermate control wild type and AβPP/PS1 mice were randomly divided into two treatment groups including control vehicle (DMSO) and picropodophyllin (PPP), a selective, competitive, and reversible IGF-1R inhibitor. The brain penetrant inhibitor was given ip. at 1 mg/kg/day. Mice were sacrificed after 7 days of daily injection and the brains, spleens, and livers were collected to quantify histologic and biochemical changes. The PPP-treated AβPP/PS1 mice demonstrated attenuated insoluble Aβ<sub>1-40/42</sub>. Additionally, an attenuation in microgliosis and protein p-tyrosine levels was observed due to drug treatment in the hippocampus. Our data suggest IGF-1R signaling is associated with disease progression in this mouse model. More importantly, modulation of the brain IGF-1R signaling pathway, even at mid-life, was enough to attenuate aspects of the disease phenotype. This suggests that small molecule therapy targeting the IGF-1R pathway may be viable for late-stage disease treatment.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020","modification":"2025-04-19T21:08:34.301Z","creation":"2025-02-19T00:50:56.596Z"},"accession":"S-EPMC7348663","cross_references":{"pubmed":["32719587"],"doi":["10.3389/fncel.2020.00200"]}}