Erol, Adnan2022-05-112022-05-1120091387-2877https://doi.org/10.3233/JAD-2009-1047https://hdl.handle.net/20.500.11776/8759Peripheral insulin resistance is associated with hyperinsulinemia, which may be associated with brain insulin deficiency that is characteristic of sporadic Alzheimer's disease (sAD). Oxidative insult, which is the result of insulin associated disordered brain energy metabolism, is a significant early event in the pathological cascade of sAD. Aggregation of disease-specific proteins such as amyloid-? and tau may act as a compensatory response against the oxidative insult at the early periods. In the later stages, oxidative stress stimulates c-Jun N-terminal kinase (JNK) activation. The deficient insulin signaling is ultimately linked to protein kinase B (Akt) pathway and subsequently glycogen synthase kinase-3 (GSK3) and forkhead transcription factors (FOXO). Peripheral insulin resistance related intense interactions between JNK, GSK3, FOXO factors, and p53, which may lead to apoptotic neuronal death, are outlined in a postulate. In light of this postulate, the importance of detailed knowledge of these common physiological processes for the opportunities of treatment that could prevent or reduce the onset of sAD is discussed as well. © 2009 - IOS Press and the authors. All rights reserved.en10.3233/JAD-2009-1047info:eu-repo/semantics/closedAccessAlzheimer's diseaseFOXOGSK3Insulin resistanceJNKP53amyloid beta proteinforkhead transcription factorglycogen synthase kinase 3insulinprotein kinase Bprotein p53stress activated protein kinasetau proteinAlzheimer diseaseapoptosisbrain metabolismhyperinsulinemiainsulin deficiencyinsulin resistancemetabolic disorderoxidative stresspriority journalprotein aggregationreviewReview Article1722672762-s2.0-6784911036319221404Q1