Abstract：
:Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly population, above 65 years of age. Multiple lines of evidence confirm the central role of 40-42 residue Abeta peptides in the pathogenesis of AD, but exact mechanisms of Abeta toxicity remain unclear. Recently, evidence has accumulated in favor of small oligomers of the Abeta42 peptide as major toxic species. Metal ions, copper(II) in particular, have been implicated in molecular mechanisms of Abeta neurotoxicity, including oxidative damage of lipid membranes. While monomeric Abeta peptides are not neurotoxic, the deep understanding of their chemical properties is prerequisite for significant progress in Alzheimer research. Monomeric Abeta40 and Abeta42 form a specific mononuclear complex with Cu(II), recruiting donor atoms within their common 16 amino acid N-terminal sequence. The formation of this complex, the exact structure of which is debated, correlates with increased Abeta toxicity. Human serum albumin (HSA) is a versatile carrier protein present, among others, in blood and cerebrospinal fluid. It binds one Cu(II) ion with a high, picomolar affinity and one Abeta molecule with a moderate, micromolar affinity. In this perspective, we present a model of interactions, which make HSA a likely guardian against Cu/Abeta toxicity in extracellular brain compartments.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Rózga M,Bal Wdoi
10.1021/tx900358jsubject
Has Abstractpub_date
2010-02-15 00:00:00pages
298-308issue
2eissn
0893-228Xissn
1520-5010journal_volume
23pub_type
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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