Naslov
Experimental approach to Alzheimer’s disease with emphasis on insulin resistance in the brain

Autori
Šalković Petrišić, Melita ; Babić Perhoč, Ana ; Homolak, Jan ; Knezović, Ana ; Osmanović Barilar, Jelena ; Riederer, Peter

Vrsta, podvrsta i kategorija rada
Poglavlja u knjigama, stručni

Knjiga
Handbook of neurotoxicity

Urednik/ci
Kostrzewa, Richard M.

Izdavač
Springer

Grad
Cham

Godina
2021

Raspon stranica
1-52

ISBN
978-3-030-71519-9

Ključne riječi
Alzheimer’s disease ; animal models ; streptozotocin ; intracerebroventricular ; Brain insulin resistance ; Cerebral glucose metabolism ; amyloid ß oligomers ; corticosterone

Sažetak
This chapter on current experimental models of Alzheimer’s disease (AD) is based on human post- mortem findings showing keystone markers for pathology within the ß-amyloid transduction cascade as well as pathology in the mechanism of phosphorylation of tau protein. Evidence for risk factors triggering this devastating disease focuses on type II diabetes. Therefore, modeling of Alzheimer’s disease aims to gain profound knowledge of these underlying mechanisms by studying experimental animal models. Here, several pharmacological models will be discussed in detail, with special emphasis on the one mirroring type II diabetes-related AD pathology induced by streptozotocin and its influences on the insulin/insulin receptor cascade in the brain as well as ß-amyloid and tau pathologies associated with cognitive impairments. While most of transgenic mouse models, like the APP Tg2576 model, demonstrate ß-amyloid plaque formation and impaired memory in rather old age, streptozotocin is able to aggravate the process of pathology so that AD pathology is seen months earlier. This indicates a profound interaction of AD pathology with the brain insulin/insulin receptor cascade and pathobiochemistry. Since this interaction is gaining more and more interest, it is here discussed in a view of a non-transgenic modeling of AD introduced lately by means of a central application of synthetic β-amyloid. Recent trend of repurposing antidiabetic drugs as possible anti-AD drugs and beneficial effects of the intranasal insulin therapy both in clinical and preclinical trials provides a strong support to the metabolic/brain insulin dysfunction-related core of sporadic AD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA