Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA, USA.
J Pept Sci. 2022 Oct;28(10):e3414. doi: 10.1002/psc.3414. Epub 2022 May 6.
Recent findings suggest that amyloid-β (Aβ) may not be the only peptidic culprit for the cognitive decline observed in patients with Alzheimer's disease. A C-terminal fragment of Aβ, amyloid-α (Aα), also known as p3, has been shown to form amyloidogenic oligomers and fibrils more rapidly than Aβ. However, the insolubility and aggregation propensity of this 24-26-residue peptide make it exceptionally difficult to produce, purify, and subsequently study. This paper reports a reproducible, multi-step method for the purification and pre-treatment of Aα and related analogues, yielding 95%-99% pure peptides. We anticipate that the methods described herein will permit previously inaccessible biophysical and biological experiments that may be critical to understanding the role of this too long overlooked peptide in AD disease pathology.
最近的研究结果表明，淀粉样蛋白-β（Aβ）可能不是阿尔茨海默病患者认知能力下降的唯一致病肽。Aβ的 C 端片段，淀粉样蛋白-α（Aα），也称为 p3，已被证明比 Aβ更快地形成淀粉样原纤维和寡聚物。然而，这种 24-26 个残基肽的不溶性和聚集倾向使其极难生产、纯化，并且随后进行研究。本文报道了一种可重复的、多步纯化和预处理 Aα 及相关类似物的方法，得到 95%-99%纯度的肽。我们预计，本文所述的方法将允许进行以前无法进行的生物物理和生物学实验，这对于理解这种长期被忽视的肽在 AD 疾病病理中的作用可能至关重要。
