Therapeutic potential of a novel multifunctional iron chelator on cognitive decicits and insulin degrading enzyme expression in a rat model of sporadic Alzheimer's disease

Ana Knezović,Marina Knapić,Peter Riederer,Jelena Osmanović-Barilar,Melita Šalković-Petrišić,Silvia Mandel,Moussa Youdim

doi:10.1186/2050-6511-13-s1-a65

Abstract

Background There is a need in modern pharmacology for a representative animal model which should accurately mimic sporadic Alzheimer’s disease (sAD), the prevailing type of dementia in humans, and thus could be suitable for novel drug testing. Rats treated intracerebroventricularly with the betacytotoxic agent streptozotocin (STZ-icv), have been proposed recently as a non-transgenic sAD model which demonstrates AD-like pathology features at cognitive, neurochemical and structural level. In addition to the cognitive deficits, pathological accumulation of amyloid b (Ab) peptide is one of the neuropathological hallmarks of sAD, and a growing body of evidence suggests the involvement of insulin degrading enzyme (IDE), responsible for Ab degradation, in sAD pathophysiology. We have explored the time course of cognitive deficits and hippocampal (HPC) IDE expression in the STZ-icv rat model of sAD, and the therapeutic potential of the novel multifunctional iron-chelating drug M30 to improve these deficits.

Highlights

There is a need in modern pharmacology for a representative animal model which should accurately mimic sporadic Alzheimer’s disease, the prevailing type of dementia in humans, and could be suitable for novel drug testing
In addition to the cognitive deficits, pathological accumulation of amyloid b (Ab) peptide is one of the neuropathological hallmarks of sporadic Alzheimer’s disease (sAD), and a growing body of evidence suggests the involvement of insulin degrading enzyme (IDE), responsible for Ab degradation, in sAD pathophysiology
We have explored the time course of cognitive deficits and hippocampal (HPC) IDE expression in the STZ-icv rat model of sAD, and the therapeutic potential of the novel multifunctional iron-chelating drug M30 to improve these deficits

Summary

Background

There is a need in modern pharmacology for a representative animal model which should accurately mimic sporadic Alzheimer’s disease (sAD), the prevailing type of dementia in humans, and could be suitable for novel drug testing. Rats treated intracerebroventricularly with the betacytotoxic agent streptozotocin (STZ-icv), have been proposed recently as a non-transgenic sAD model which demonstrates AD-like pathology features at cognitive, neurochemical and structural level. In addition to the cognitive deficits, pathological accumulation of amyloid b (Ab) peptide is one of the neuropathological hallmarks of sAD, and a growing body of evidence suggests the involvement of insulin degrading enzyme (IDE), responsible for Ab degradation, in sAD pathophysiology. We have explored the time course of cognitive deficits and hippocampal (HPC) IDE expression in the STZ-icv rat model of sAD, and the therapeutic potential of the novel multifunctional iron-chelating drug M30 to improve these deficits

Methods

Results

Conclusions