Unraveling the molecular mechanisms behind the metabolic basis of sporadic alzheimer's disease
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Dosyalar
Tarih
2009
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
IOS Press
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Peripheral 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.
Açıklama
Anahtar Kelimeler
Alzheimer's disease, FOXO, GSK3, Insulin resistance, JNK, P53, amyloid beta protein, forkhead transcription factor, glycogen synthase kinase 3, insulin, protein kinase B, protein p53, stress activated protein kinase, tau protein, Alzheimer disease, apoptosis, brain metabolism, hyperinsulinemia, insulin deficiency, insulin resistance, metabolic disorder, oxidative stress, priority journal, protein aggregation, review
Kaynak
Journal of Alzheimer's Disease
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
17
Sayı
2
