The Mental Health Research Institute, Parkville, VIC, Australia.
Int J Biochem Cell Biol. 2010 Dec;42(12):1915-8. doi: 10.1016/j.biocel.2010.08.015. Epub 2010 Sep 15.
The accumulation of amyloid-beta (Aβ) peptides is believed to be a central contributor to the neurodegeneration typically seen in Alzheimer's disease (AD) brain. Aβ extracted from AD brains invariably possesses extensive truncations, yielding peptides of differing N- and C-terminal composition. Whilst Aβ is often abundant in the brains of cognitively normal elderly people, the brains of AD patients are highly enriched for N-terminally truncated Aβ bearing the pyroglutamate modification. Pyroglutamate-Aβ (pE-Aβ) has a higher propensity for oligomerisation and aggregation than full-length Aβ, potentially seeding the accumulation of neurotoxic Aβ oligomers and amyloid deposits. In addition, pE-Aβ has increased resistance to clearance by peptidases, causing these peptides to persist in biological fluids and tissues. The extensive deposition of pE-Aβ in human AD brain is under-represented in many transgenic mouse models of AD, reflecting major differences in the production and processing of Aβ peptides in these models compared to the human disease state.
淀粉样蛋白-β (Aβ) 肽的积累被认为是阿尔茨海默病 (AD) 大脑中常见的神经退行性变的主要原因。从 AD 大脑中提取的 Aβ 通常具有广泛的截断，产生不同 N-和 C-末端组成的肽。虽然 Aβ 在认知正常的老年人的大脑中经常丰富，但 AD 患者的大脑中富含具有焦谷氨酸修饰的 N 端截断的 Aβ。焦谷氨酸-Aβ (pE-Aβ) 比全长 Aβ更容易发生寡聚化和聚集，可能会引发神经毒性 Aβ 寡聚物和淀粉样沉积物的积累。此外，pE-Aβ 对肽酶的清除具有更高的抵抗力，导致这些肽在生物体液和组织中持续存在。在许多 AD 的转基因小鼠模型中，人类 AD 大脑中 pE-Aβ 的广泛沉积被低估了，这反映了这些模型中 Aβ 肽的产生和加工与人类疾病状态存在重大差异。
