β-Amyloid fibrils catalyze neurotransmitter degradation
β-Amyloid fibrils catalyze neurotransmitter degradation
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DOI：
10.1016/j.checat.2021.07.005
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发表时间：
2021-09-16
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影响因子：
--
通讯作者：
Jelinek, Raz
中科院分区：
文献类型：
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作者：
Arad, Elad;Leshem, Avigail Baruch;Jelinek, Raz
淀粉样原纤维是阿尔茨海默病（AD）的标志之一，尽管斑块形成淀粉样原纤维和AD病理学之间的因果关系仍有待澄清。这项研究首次证明，对于天然存在的淀粉样蛋白，包含42个残基的淀粉样蛋白-b肽（A β 42）的原纤维表现出显著的催化性质。β 42纤维催化模型酯对硝基苯乙酸酯（pNPA）和乙酰硫代胆碱（神经递质乙酰胆碱的替代品）的水解。A β 42纤维还催化了主要神经递质多巴胺和肾上腺素的氧化。重要的是，催化活性是由成熟的A β 42原纤维而不是肽单体或寡聚A β 42（推定的神经毒性物质）具体表现的。此外，最大催化活性由全长A β 42原纤维记录，而包含A β 42亚结构域的原纤维组装体的催化性显著较低。Ab原纤维的催化活性可能在AD病理生理学中表现出潜在的作用。
Amyloid fibrils are one of the hallmarks of Alzheimer's disease (AD), although a causative link between plaque-forming amyloid fibrils and AD pathology remains to be clarified. This study demonstrates, for the first time for a naturally occurring amyloid, that fibrils comprising the 42-residue amyloid-b peptide (A beta 42) exhibit significant catalytic properties. A beta 42 fibrils catalyzed the hydrolysis of the model ester para-nitrophenyl acetate (pNPA) and of acetylthiocholine, a surrogate for the neurotransmitter acetylcholine. A beta 42 fibrils also catalyzed oxidation of the prominent neurotransmitters dopamine and adrenaline. Importantly, the catalytic activity was specifically manifested by mature A beta 42 fibrils and not the peptide monomers or oligomeric A beta 42, the putative neurotoxic species. Furthermore, maximal catalytic activity was recorded by the fulllength A beta 42 fibrils, whereas fibrillar assemblies comprising A beta 42 subdomains were significantly less catalytic. The catalytic activity of Ab fibrils could exhibit insidious roles in AD pathophysiology.