F. F.B. Hatip, I. Hatip-Al-Khatib, Y. Matsunaga, M. Suenaga and N. Sen Pages 602 - 614 ( 13 )
Amyloid β-protein (Aβ) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimers disease. Blocking this process could have a therapeutic value. β-sheet breaker peptides (βSBP) decrease Aβ fibrillogenesis and neurotoxicity by preventing or dissolving misfolded Aβ aggregates. The present study investigated the effects of SBPs on A 40-related neuropathology, memory impairment in 8-armed radial maze and expression of A 40 in brain and serum. A 40 was injected into amygdaloid nucleus followed 8 days later by octapeptide 7bgr;SBPs 15-22, 16-23 and 17-24. Aβ40 was detected not only in amygdala, but also in serum. Aβ40 induced cellular changes in amygdala and additionally in hippocampus. A7bgr;40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The βSBPs decreased Aβ40-induced pathological changes, memory impairment and Aβ40 expression in serum. The 7bgr;SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide βSBPs corrected Aβ40-induced memory impairment, and support investigation of βSBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimers disease.
Amyloid-β40 peptide, β-sheet breaker peptide, amygdala, hippocampus, memory, Alzheimer’s disease.
Pamukkale University, Faculty of Medicine, Division of Internal Medicine, Department of Pharmacology, Kinikli Campus, Denizli 20070, Turkey.