通过血液分析诊断阿尔茨海默病的新方法
![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病的新方法](https://scx1.b-cdn.net/csz/news/800a/2022/novel-way-to-diagnose.jpg)
利用蛋白质组学和其他先进的分子生物学工具,由卡罗林斯卡学院的一个小组领导的国际研究团队发现了一种通过血液分析诊断阿尔茨海默病的新方法,有可能揭示疾病的潜在原因并预防其发展。
当我们变老时,我们体内的蛋白质也会变老,包括血液中的长寿蛋白质,比如白蛋白。蛋白质老化的主要表现之一是氨的损失,称为脱酰胺。随着脱酰胺产物的积累蛋白质分子失去了它的结构、功能和溶解性,开始聚集。
去酰胺化和神经退行性变之间的联系早已被假定,但直到现在才获得决定性的证据。由Roman Zubarev, MBB领导的一个国际研究小组发现,阿尔茨海默病(AD)的发展不仅与脱酰胺白蛋白的积累有关,而且还与天然脱酰胺特异性抗体对脱酰胺的防御能力减弱有关。在阿尔茨海默病中,血液蛋白的去酰胺化似乎先于所有其他损害过程,与之对抗可能会防止神经退行性变并延长健康寿命。这项研究发表在阿尔茨海默氏症.
进一步探索
更多信息:王吉晶等,异天冬氨酸与阿尔茨海默病病因学之间的联系,阿尔茨海默氏症(2022)。DOI: 10.1002 / alz.12735
所提供的卡罗林斯卡医学院
引用:通过血液分析诊断阿尔茨海默病的新方法(2022,8月8日)检索于2022年9月24日从//www.puressens.com/news/2022-08-alzheimer-disease-blood-analysis.html
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