Evidence that a synthetic amyloid-脽 oligomer-binding peptide (ABP) targets amyloid-脽 deposits in transgenic mouse brain and human Alzheimer鈥檚 disease brain

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• 作者：Balu Chakravarthy ; ^{Balu.Chakravarthy@nrc-cnrc.gc.ca" class="auth_mail} ; Shingo Ito ; Trevor Atkinson ; Chantal Gaudet ; Michel M&eacute ; nard ; Leslie Brown ; James Whitfield
• 关键词：Alzheimer&rsquo ; s disease ; A尾1&ndash ; 42 oligomers ; AD transgenic mice ; Human AD brains ; PCM-1 protein ; Amyloid binding peptide
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：14 March, 2014
• 年：2014
• 卷：445
• 期：3
• 页码：656-660
• 全文大小：1615 K

文摘

The synthetic 鈭? kDa ABP (amyloid-脽 binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro A尾_1-42 oligomers, believed to be key co-drivers of Alzheimer鈥檚 disease (AD), but not monomers (Chakravarthy et al., (2013) ). ABP also prevents A脽_1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering A脽 oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds A尾_1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets A尾_1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice.