Scholarly record

AMYLOID-? AND ANTI-AMYLOID PEPTIDES INVOLVED IN ALZHEIMER`S DISEASE: INTERACTIONS WITH METAL IONS

Laura Ion

Abstract

Alzheimer`s diseases (AD) is the most common age-related dementia, being characterized by accumulation of extracellular amyloid plaques in AD brains. The principal constituent of these plaques are fibrils which are primarily composed of amyloid-? peptides (A?), with 39-42 amino acid residues in length, which are the proteolysis products derived from the amyloid precursor peptide (APP). Several factors, such as oxidative stress, inflammation, metal ions or genetic factors are associated with AD. Even if metal ions are involved in many biological and biomedical processes, several studies suggest that copper, zinc, iron, aluminum, etc. are implicated in neurotoxicity of A? peptides. Beside the interest in studying the AD biochemical process, there is also a high interest in studying the anti-amyloid peptides, such as the NAP peptide, due to their neuroprotective activities. Here, we report on the synthesis of both amyloid-? peptides and neuroprotective peptides that interact with several metal ions. Both peptides and their complexes with metals have been characterized by mass spectrometry (MS), infrared spectroscopy (FT-IR) and atomic force microscopy (AFM). Therefore, we synthesized by solid phase peptide synthesis procedure, the native A?1-16 (1DAEFRHDSGYEVHHQK16) peptide, 2 mutated A?1-16 peptides, in which His6,13,14 residues were replaced by serine (A?(S6,13,14)1-16: 1DAEFRSDSGYEVSS-QK16) and alanine (A?(A6,13,14)1-16: 1DAEFRADSGYEVAAQK16) as well as the NAP peptide (1NAPVSIPQ8) and three of its analogs with glycine (NAPG: 1NAPVGIPQ8), alanine (NAPA: 1NAPVAIPQ8) and histidine (NAPH: 1NAPVHIPQ8). Our mass spectrometric data and, especially the MS/MS ones show that all peptides interact with the metal ions studied and suggest that the formation of complex between metal ions and peptides depends on the type of metal used as well as the amino acid residues involved in metal binding. The AFM images indicate that the more hydrophobic A?(Ala)1-16 forms easier fibrils than the native A? peptide in the presence of metal ions, especially aluminum or even as a free peptide.

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