{"doi":"10.3389/fncel.2020.00200","title":"IGF-1R Inhibitor Ameliorates Neuroinflammation in an Alzheimer’s Disease Transgenic Mouse Model","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 Aβ1-40/42 concentrations were observed in this mouse model. This supported the hypothesis that IGF-1 may contribute to progression of 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 2 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 1mg/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 Aβ1-40/42 and pro-inflammatory cytokine levels in the temporal cortex including eotaxin, TNF-, IL-1, and IL-1. Additionally, an attenuation in microgliosis and protein p-tyrosine levels were observed due to drug treatment in the hippocampus. Our data suggests 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 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","year":2020,"id":67369,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":357672,"name":"Angela M. Floden","orcid":null,"position":1,"is_corresponding":false},{"id":356730,"name":"Gunjan D. Manocha","orcid":"0000-0003-4488-6627","position":2,"is_corresponding":false},{"id":272291,"name":"Marilyn G. Klug","orcid":"0000-0001-8476-7097","position":3,"is_corresponding":false},{"id":272292,"name":"Colin K. Combs","orcid":"0000-0001-8671-5880","position":4,"is_corresponding":false},{"id":356729,"name":"Mona Sohrabi","orcid":"0000-0001-8707-8756","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"32719587","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}