查看文章

Brain cholesterol plays a critical role in Alzheimer’s disease and other neurodegenerative diseases. The molecular mechanisms linking cholesterol to neurotoxicity have remained elusive for a long time, but recent data have allowed the identification of functional cholesterol-binding domains in several amyloidogenic proteins involved in neurodegenerative diseases, including Alzheimer’s disease. In this review, we analyze the cholesterol binding properties of β-amyloid (Aβ) peptides and the impact of these interactions on amyloid pore formation. We show that although the cholesterol-binding domains of Aβ peptides and of transmembrane precursor C99 are partially overlapping, they involve distinct amino acid residues, so that cholesterol has a greater affinity for Aβ than for C99. Synthetic 22–35 and 25–35 fragments of Aβ retained the ability of the full-length peptide 1–42 to bind cholesterol and to form zinc …