Effects of 8-residue β sheet breaker peptides on aged Aβ40-induced memory impairment and Aβ40 expression in rat brain and serum following intraamygdaloid injection.
Amyloidβ-protein (Aβ) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's 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 βSBPs on Aβ40-related neuropathology, memory impairment in 8-armed radial maze and expression of Aβ40 in brain and serum. Aβ40 was injected into amygdaloid nucleus followed 8 days later by octapeptideβSBPs 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. Aβ40 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 βSBP15-22 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 Alzheimer's disease.
Pamukkale University, Faculty of Medicine, Division of Internal Medicine, Department of Pharmacology, Kinikli Campus, Denizli 20070, Turkey. fundabolukbasi@yahoo.com
F F B
FF
Hatip
I
I
Hatip-Al-Khatib
Y
Y
Matsunaga
M
M
Suenaga
N
N
Sen
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)