Amyloid β-Protein (25-35) amide

Amyloid β-Protein (25-35) amide is a product of the amidation of amyloid-β (Aβ), in which the ability to generate Aβ is strongly reduced^[1]. Amyloid β-Protein (25-35) amide is a modified fragment sequence of the Aβ peptide, consisting of amino acids 25-35, with the C-terminus blocked by an amide bond^[2]. The amino acid sequence of Aβ (25-35) peptide is NH2-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-COOH, where the first Gly represents amino acid 25 and the last Met represents amino acid 35^[3]. Aβ is neurotoxic, but the strength of the toxicity is not related to its aggregation state. Aβ oligomers also show neurotoxicity and cause neuronal damage^{[4, 5]}. Aβ is involved in the pathogenesis of Alzheimer's disease and is present in neurons of the subiculum and entorhinal cortex of Alzheimer's brain samples and inclusion body myositis (IBM) muscles. It binds to receptors present in microglia and is able to insert into lipid membranes^[6].

References:
[1] Li H, Rahimi F, Bitan G. Modulation of amyloid β-protein (Aβ) assembly by homologous C-terminal fragments as a strategy for inhibiting Aβ toxicity[J]. ACS chemical neuroscience, 2016, 7(7): 845-856.
[2] Ghosh N, Kundu L M. Breaker peptides against amyloid-β aggregation: a potential therapeutic strategy for Alzheimer’s disease[J]. Future Medicinal Chemistry, 2021, 13(20): 1767-1794.
[3] Cheung N S, Small D H, Livett B G. An Amyloid Peptide, βA4 25–35, Mimics the Function of Substance P on Modulation of Nicotine‐Evoked Secretion and Desensitization in Cultured Bovine Adrenal Chromaffin Cells[J]. Journal of neurochemistry, 1993, 60(3): 1163-1166.
[4] Aleksis R, Oleskovs F, Jaudzems K, et al. Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity[J]. Biochimie, 2017, 140: 176-192.
[5] Rahimi F, Li H, Sinha S, et al. Modulators of amyloid β-protein (Aβ) self-assembly[M]//Developing Therapeutics for Alzheimer's Disease. Academic Press, 2016: 97-191.
[6] Millucci L, Ghezzi L, Bernardini G, et al. Conformations and biological activities of amyloid beta peptide 25-35[J]. Current Protein and Peptide Science, 2010, 11(1): 54-67.

Amyloid β-Protein (25-35) amide是β淀粉样蛋白（amyloid-β，Aβ）酰胺化的一种产物，其中β淀粉样蛋白的生成能力已被强烈降低^[1]。Amyloid β-Protein (25-35) amide是β淀粉样肽的修饰片段序列，由25-35位氨基酸组成，C端被酰胺键封闭^[2]。Aβ (25-35) 肽的氨基酸序列为 NH2-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-COOH，其中第一个Gly代表氨基酸25，最后一个Met代表氨基酸35^[3]。Aβ具有神经毒性，但毒性强弱与其聚集状态无关，Aβ寡聚体也表现出神经毒性并导致神经元损伤^{[4, 5]}。Aβ参与阿尔茨海默病的发病机制，存在于阿尔茨海默氏症大脑样本和包涵体肌炎（IBM）肌肉的下托和内嗅皮层神经元中，它与小胶质细胞中存在的受体结合，并且能够插入脂质膜^[6]。