肌肽改善与淀粉样蛋白 (Aβ) 二级结构的神经病理学改变相关的衰老引起的认知障碍和大脑区域神经变性,Journal of Neurochemistry

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肌肽改善与淀粉样蛋白 (Aβ) 二级结构的神经病理学改变相关的衰老引起的认知障碍和大脑区域神经变性
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2021-03-26 , DOI: 10.1111/jnc.15357
Soumyabrata Banerjee _{1,

2} , Biswajit Mukherjee ₁ , Mrinal K Poddar ₁ , Gary L Dunbar ₂

Affiliation

衰老引起的蛋白质病，包括淀粉样蛋白 β (Aβ) 构象的恶化，与内源性肌肽水平的降低和认知障碍有关。肌肽是一种众所周知的内源性抗氧化剂，可抵抗衰老诱导的 Aβ 斑块形成。本研究的目的是研究外源性肌肽治疗对衰老引起的变化的影响 (a) 内源性肌肽稳态水平和不同大脑区域 (大脑皮层、海马、下丘脑、脑桥髓质和小脑）和（b）认知功能。用肌肽（2.0 μg kg ^-1 天^-1; 它）或等效体积的载体（盐水）连续 21 天，并使用 8 臂径向迷宫测试进行认知测试。处理大脑以使用拉曼光谱评估 Aβ 斑块的构象完整性，并使用 HPLC 测量大脑区域中肌肽的内源性水平。结果表明，肌肽治疗改善了衰老引起的认知功能缺陷，减少了 Aβ 蛋白二级结构中的 β-折叠，并减轻了所检查大脑区域中肌肽和脊柱密度稳态水平的降低. 因此，这些结果表明肌肽可以减轻衰老引起的：

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Carnosine improves aging-induced cognitive impairment and brain regional neurodegeneration in relation to the neuropathological alterations in the secondary structure of amyloid beta (Aβ)

Aging-induced proteinopathies, including deterioration of amyloid beta (Aβ) conformation, are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well-known endogenous antioxidant, which counteracts aging-induced Aβ plaque formation. The aim of this study was to investigate the effects of exogenous carnosine treatments on aging-induced changes (a) in the steady-state level of endogenous carnosine and conformation of Aβ secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons-medulla, and cerebellum) and (b) cognitive function. Young (4 months) and aged (18 and 24 months) male albino Wistar rats were treated with carnosine (2.0 μg kg⁻¹ day⁻¹; i.t.) or equivalent volumes of vehicle (saline) for 21 consecutive days and were tested for cognition using 8-arm radial maze test. Brains were processed to assess the conformational integrity of Aβ plaques using Raman spectroscopy and endogenous levels of carnosine were measured in the brain regions using HPLC. Results indicated that carnosine treatments improved the aging-induced deficits in cognitive function and reduced the β-sheets in the secondary structure of Aβ protein, as well as mitigating the reduction in the steady-state levels of carnosine and spine density in the brain regions examined. These results thus, suggest that carnosine can attenuate the aging-induced: (a) conformational changes in Aβ secondary structure by reducing the abundance of β-sheets and reductions in carnosine content in the brain regions and (b) cognitive impairment.

更新日期：2021-03-26

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