Naslov
Streptozotocin-induced experimental model of sporadic Alzheimer's disease as a tool for testing novel therapeutic approaches in this disease

Autori
Šalković-Petrišić, Melita ; Knezović, Ana ; Riderer, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Neurologia Croatica / - , 2012, 90-90

Skup
6th Croatian Congress on Alzheimer's disease

Mjesto i datum
Primošten, Hrvatska, 10.10.2012. - 13.10.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
drug testing; Alzheimer's disease; streptozotocin

Sažetak
BACKGROUND. None of the novel compounds tested in clinical trials for the therapeutic potential against the Alzheimer's disease (AD) has been approved until now. Failure to accurately predict clinical efficacy can result from a number of causes including the use of inaccurate models of disease. It is difficult to establish an experimental animal model that would faithfully mimic the developmental pathology of the prevailing sporadic form of Alzheimer’s disease (sAD) in humans. Widely exploited transgenic mice AD models resemble the rare familial form of AD and are, thus inappropriate models for testing novel therapeutic approaches in sAD treatment. In line with accumulating evidence linking sAD with underlying development of insulin resistant brains state (IRBS), a new, non-transgenic, animal model has been proposed as a representative model of sAD. The model is developed by intracerebroventricular application of the betacytotoxic drug streptozotocin (STZ-icv) which in rats and mice results in IRBS development. STZ-icv model demonstrates cognitive and cholinergic deficits, glucose hypometabolism and oxidative stress as well as markers of neurodegeneration in the brain that resemble those found in sAD patients. AIM AND METHODS. By means of PUBMED search for therapeutic strategies (excluding Indian and Chinese herbal drugs) tested in STZ-icv model and published until April 2012, we aimed to evaluate the efficacy of the tested strategies and compare it with their efficacy in clinical AD trials. RESULTS. In total 10 therapeutic strategies (drugs with predominant antioxidant and anti-inflammatory activity, respectively, cholinesterase inhibitors, mematine, lipid-lowering drugs, antihypertensive drugs, anti-diabetic drugs, inhibitors of glycogen synthase kinase-3, estrogen-replacement therapy and physical exercise) were tested in 56 experiments on STZ-icv model. The most frequently tested were drugs with predominant antioxidative activity, and the most frequent treatment-induced improvement was found in cognition associated with improvement in cholinergic transmission and antioxidant activity. Fifty out of 56 experiments demonstrated therapeutic effectiveness in STZ-icv model and only 62% of these strategies were tested in humans until now demonstrating efficacy or partial efficacy in 77% of clinical trials. CONCLUSION. STZ-icv non-transgenic sAD model represents a promising experimental tool for testing the novel etiopathogenic and therapeutic approaches in this disease. Supported by UKF, MZOS and DAAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA