Current Alzheimer Research

Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA

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Effects of 8-Residue Beta Sheet Breaker Peptides on Aged Aβ40 – Induced Memory Impairment and Aβ40 Expression in Rat Brain and Serum Following Intraamygdaloid Injection

Author(s): F. F.B. Hatip, I. Hatip-Al-Khatib, Y. Matsunaga, M. Suenaga, N. Sen.

Abstract:

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.

Keywords: Amyloid-β40 peptide, β-sheet breaker peptide, amygdala, hippocampus, memory, Alzheimer's disease, senile plaques, fibrillogenesis, phosphorylation, LPFFD, VESYVPLFP, Stereotaxic Surgery, ELISA, dot blotting, haematoxylin, eosin, Eight-Arm Radial maze Test, Tukey test, ANOVA, karyolysis, astrocytosis, microgliosis, KLVFF, TEF LPFFD-OH, LPYFD-NH2, dementia, maze test

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Article Details

VOLUME: 7
ISSUE: 7
Year: 2010
Page: [602 - 614]
Pages: 13
DOI: 10.2174/156720510793499048
Price: $58