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阿尔茨海默病早期诊断中有前景的蛋白质生物标志物。

Promising protein biomarkers in the early diagnosis of Alzheimer's disease.

机构信息

Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan, 173229, India.

Department of Humanities & Social Sciences, Indian Institute of Technology Roorkee, Roorkee, 247667, India.

出版信息

Metab Brain Dis. 2022 Aug;37(6):1727-1744. doi: 10.1007/s11011-021-00847-9. Epub 2022 Jan 11.

Abstract

Alzheimer's disease (AD) is an insidious, multifactorial disease that involves the devastation of neurons leading to cognitive impairments. Alzheimer's have compounded pathologies of diverse nature, including proteins as one important factor along with mutated genes and enzymes. Although various review articles have proposed biomarkers, still, the statistical importance of proteins is missing. Proteins associated with AD include amyloid precursor protein, glial fibrillary acidic protein, calmodulin-like skin protein, hepatocyte growth factor, matrix Metalloproteinase-2. These proteins play a crucial role in the AD hypothesis which includes the tau hypothesis, amyloid-beta (Aβ) hypothesis, cholinergic neuron damage, etc. The present review highlights the role of major proteins and their physiological functions in the early diagnosis of AD. Altered protein expression results in cognitive impairment, synaptic dysfunction, neuronal degradation, and memory loss. On the medicinal ground, efforts of making anti-amyloid, anti-tau, anti-inflammatory treatments are on the peak, having these proteins as putative targets. Few proteins, e.g., Amyloid precursor protein results in the formation of non-soluble sticky Aβ and Aβ monomers that, over time, aggregate into plaques in the cortical and limbic brain areas and neurogranin is believed to regulate calcium-mediated signaling pathways and thus modulating synaptic plasticity are few putative and potential forthcoming targets for developing effective anti-AD therapies. These proteins may help to diagnose the disease early, bode well for the successful discovery and development of therapeutic and preventative regimens for this devasting public health problem.

摘要

阿尔茨海默病(AD)是一种隐匿的、多因素的疾病,涉及神经元的破坏,导致认知障碍。AD 具有多种性质的复合病理学,包括蛋白质作为一个重要因素,以及突变基因和酶。尽管各种综述文章提出了生物标志物,但蛋白质的统计学重要性仍然缺失。与 AD 相关的蛋白质包括淀粉样前体蛋白、神经胶质纤维酸性蛋白、钙调蛋白样皮肤蛋白、肝细胞生长因子、基质金属蛋白酶-2。这些蛋白质在 AD 假说中起着至关重要的作用,包括 tau 假说、淀粉样β(Aβ)假说、胆碱能神经元损伤等。本综述强调了主要蛋白质及其生理功能在 AD 早期诊断中的作用。蛋白质表达的改变导致认知障碍、突触功能障碍、神经元降解和记忆丧失。在医学领域,针对淀粉样蛋白、tau 蛋白、抗炎治疗的抗蛋白药物的研发正在如火如荼地进行,这些蛋白质被认为是潜在的靶点。少数蛋白质,如淀粉样前体蛋白,导致形成不溶性粘性 Aβ和 Aβ单体,随着时间的推移,这些单体在皮质和边缘脑区聚集形成斑块,神经颗粒蛋白被认为调节钙介导的信号通路,从而调节突触可塑性,是开发有效抗 AD 治疗方法的潜在靶点。这些蛋白质可能有助于早期诊断疾病,为成功发现和开发针对这一严重公共卫生问题的治疗和预防方案提供良好的前景。

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