Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer's Disease and Inhibitors of Amyloid Formation.
Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer's Disease and Inhibitors of Amyloid Formation.
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DOI：
10.3390/biom13010167
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发表时间：
2023-01-13
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
（1）背景和目的：β淀粉样蛋白（Aβ42）聚集引起的淀粉样变性是阿尔茨海默病（AD）的关键致病事件，而人类胰岛中成熟胰岛淀粉样多肽（IAPP37）的聚集导致β细胞功能障碍。这项研究的目的是发现潜在的生物标志物，这些标志物可能另外为早期 AD 患者的治疗指明方向。 (2) 方法：我们使用生物信息学方法来发现新的 IAPP 亚型，并开发了一种定量选择性反应监测 (SRM) 蛋白质组学测定法来测量早期 AD 个体和对照个体的人血浆和脑脊液中的肽水平，以及临床确诊的 AD 和对照个体的死后大脑中的肽水平。我们使用硫磺素 T 淀粉样蛋白报告基因测定来测量 IAPP 同工型纤维颤动倾向以及针对 Aβ42 和 IAPP37 聚集的抗淀粉样蛋白潜力。 (3) 结果：我们发现了原始人类特异性的 IAPP 亚型：hIAPPβ（编码延长的前肽）和 hIAPPγ（被加工成成熟的 IAPP25 而不是 IAPP37）。我们发现 AD 患者血浆中 hIAPPβ 显着减少，准确度为 89%。我们发现 IAPP25 和 GDNF 衍生的 DNSP11 是抑制 IAPP37 和 Aβ42 聚集的非聚集肽。 (4)结论：源自hIAPP亚型的新型肽有潜力作为早期AD的血源性生物标志物，并被开发为基于肽的抗淀粉样蛋白药物。
(1) Background and aims: Amyloidosis due to aggregation of amyloid-β (Aβ42) is a key pathogenic event in Alzheimer’s disease (AD), whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islets leads to β-cell dysfunction. The aim of this study is to uncover potential biomarkers that might additionally point to therapy for early AD patients. (2) Methods: We used bioinformatic approach to uncover novel IAPP isoforms and developed a quantitative selective reaction monitoring (SRM) proteomic assay to measure their peptide levels in human plasma and CSF from individuals with early AD and controls, as well as postmortem cerebrum of clinical confirmed AD and controls. We used Thioflavin T amyloid reporter assay to measure the IAPP isoform fibrillation propensity and anti-amyloid potential against aggregation of Aβ42 and IAPP37. (3) Results: We uncovered hominid-specific IAPP isoforms: hIAPPβ, which encodes an elongated propeptide, and hIAPPγ, which is processed to mature IAPP25 instead of IAPP37. We found that hIAPPβ was significantly reduced in the plasma of AD patients with the accuracy of 89%. We uncovered that IAPP25 and a GDNF derived DNSP11 were nonaggregating peptides that inhibited the aggregation of IAPP37 and Aβ42. (4) Conclusions: The novel peptides derived from hIAPP isoforms have potential to serve as blood-derived biomarkers for early AD and be developed as peptide based anti-amyloid medicine.
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影响因子：
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作者：
Bhowmick DC;Singh S;Trikha S;Jeremic AM
通讯作者：
Jeremic AM
DOI：
10.1007/s00259-021-05253-y
发表时间：
2021-07
影响因子：
9.1
作者：
Ashton NJ;Leuzy A;Karikari TK;Mattsson-Carlgren N;Dodich A;Boccardi M;Corre J;Drzezga A;Nordberg A;Ossenkoppele R;Zetterberg H;Blennow K;Frisoni GB;Garibotto V;Hansson O
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Hansson O
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DOI：
10.1016/j.jalz.2018.09.010
发表时间：
2019-03
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
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作者：
Chen Z;Mengel D;Keshavan A;Rissman RA;Billinton A;Perkinton M;Percival-Alwyn J;Schultz A;Properzi M;Johnson K;Selkoe DJ;Sperling RA;Patel P;Zetterberg H;Galasko D;Schott JM;Walsh DM
通讯作者：
Walsh DM
影响因子：
3.5
作者：
CHRISTMANSON, L;RORSMAN, F;BETSHOLTZ, C
通讯作者：
BETSHOLTZ, C
影响因子：
3
作者：
Fuqua, Joshua L.;Littrell, Ofelia M.;Gerhardt, Greg A.
通讯作者：
Gerhardt, Greg A.