通过血液分析诊断阿尔茨海默氏病的新方法
![IsoAsp formation and the updated isoAsp hypothesis of AD. (A) Formation of isoAsp via succinimide intermediate by deamidation of Asn or isomerization of Asp residues, and its “repair” by the enzyme PIMT that methylates isoAsp using SAM as a methyl donor, converting it to SAH. Methylated isoAsp spontaneously loses a methanol molecule to become either normal l-Asp (in ≤25% cases) or isoAsp again. (B) The updated isoAsp hypothesis of AD: Aβ peptide and p-tau protein produced in brain are cleared by passing via the blood-brain barrier and being carried by HSA to kidneys and liver. Spontaneously deamidated HSA is repaired in liver; failure of repair leads to HSA aggregation, with a lost ability to bind Aβ and p-tau. The anti-isoAsp antibodies remove deamidated HSA, and newly synthesized HSA molecules restore homeostasis. Due to a combination of insufficient repair and reduced removal of deamidated HSA, the diminished clearance of Aβ and p-tau causes their accumulation in brain, with the Aβ oligomers and ultimately plaques as well as neurofibrillary tangles formed, resulting in AD. Image was created via BioRender. Abbreviations: IsoAsp, isoaspartate; Asn, asparagine; Asp, aspartate; PIMT, l-isoaspartyl methyltransferase; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; AD, Alzheimer's disease; HSA, human serum albumin; Aβ, amyloid beta; p-tau, phosphorylated tau; NFTs, neurofibrillary tangles; Ab, antibody. Credit: <i>Alzheimer's & Dementia</i> (2022). DOI: 10.1002/alz.12735 通过血液分析诊断阿尔茨海默氏病的新方法](https://scx1.b-cdn.net/csz/news/800a/2022/novel-way-to-diagnose.jpg)
使用蛋白质组学和其他分子生物学的高级工具,由Karolinska Institutet的一组研究人员团队通过血液分析找到了一种诊断阿尔茨海默氏病的新方法。
当我们老化时,我们体内的蛋白质也是如此,包括血液中的长寿命蛋白,例如白蛋白。蛋白质衰老的主要表现之一是氨的丧失,称为脱氨酸。随着脱氨酸产品的积累,蛋白质分子失去其结构,功能和溶解度,并开始聚集。
长期以来,脱氨酸与神经退行性之间的联系已被假设,但直到现在才获得了决定性的证据。正如由罗马·祖巴雷夫(Roman Zubarev)领导的国际研究人员发现的那样,MBB的发展,阿尔茨海默氏病(AD)的发展不仅与脱氨基白蛋白的堆积有关,而且还与自然脱氨基特异性抗体形式的防御性脱氨酸的减少有关。由于血液蛋白的脱氨酸似乎是AD中所有其他破坏性过程之前的,因此与其积累作斗争可能会防止神经退行性变化并延长健康的健康。该研究发表在阿尔茨海默氏症和痴呆症。
进一步探索
更多信息:Jijing Wang等人,测试同甲酸和阿尔茨海默氏病病因学之间的联系,阿尔茨海默氏症和痴呆症(2022)。doi:10.1002/alz.12735
由...提供Karolinska Institutet
引用:通过血液分析诊断阿尔茨海默氏病的新颖方法(2022年8月8日)2022年8月29日从//www.pyrotek-europe.com/news/2022-08-08-alzheimer-disease-blood-analyasis.html
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