Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Perspective

血源性胰淀素，阿尔茨海默病的治疗靶点

卷 19, 期 14, 2022

发表于: 10 March, 2023

页: [905 - 908] 页: 4

弟呕挨: 10.2174/1567205020666230217091540

摘要

阿尔茨海默病 (AD) 病理学与 β 淀粉样蛋白 (Aβ) 和神经原纤维 tau 缠结的脑积聚有关。一个有趣的问题是，独立于 Aβ 和 tau 病理的靶向因子是否可以延迟甚至阻止神经变性。胰淀素是一种与胰岛素共同分泌的胰腺激素，被认为在中枢调节饱腹感中发挥作用，并被证明可在 2 型糖尿病患者中形成胰腺淀粉样蛋白。越来越多的证据表明，在散发性和早发性家族性 AD 中，胰腺分泌的形成淀粉样蛋白的胰淀素与大脑中的血管和实质 Aβ 协同聚集。 AD 模型大鼠中形成淀粉样蛋白的人胰淀素的胰腺表达加速了 AD 样病理，而基因抑制的胰淀素分泌可防止 AD 效应。因此，目前的数据表明形成胰腺淀粉样蛋白的胰淀素在改变 AD 中的作用；需要进一步的研究来测试在 AD 发病早期降低循环胰淀素水平是否可以抑制认知能力下降。

关键词: 脑积聚淀粉样蛋白β（Aβ），阿尔茨海默病（AD），血源性胰淀粉样蛋白，神经原纤维 tau 缠结，神经变性，血源性。

Next »
[1]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[2]
Scheltens P, Blennow K, Breteler MMB, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[3]
Kahn SE, D’Alessio DA, Schwartz MW, et al. Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells. Diabetes 1990; 39(5): 634-8.
[http://dx.doi.org/10.2337/diab.39.5.634] [PMID: 2185112]
[4]
Westermark P, Andersson A, Westermark GT. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev 2011; 91(3): 795-826.
[http://dx.doi.org/10.1152/physrev.00042.2009] [PMID: 21742788]
[5]
Lutz TA. Control of energy homeostasis by amylin. Cell Mol Life Sci 2012; 69(12): 1947-65.
[http://dx.doi.org/10.1007/s00018-011-0905-1] [PMID: 22193913]
[6]
Banks WA, Kastin AJ. Differential permeability of the blood-brain barrier to two pancreatic peptides: Insulin and amylin. Peptides 1998; 19(5): 883-9.
[http://dx.doi.org/10.1016/S0196-9781(98)00018-7] [PMID: 9663454]
[7]
Maianti JP, McFedries A, Foda ZH, et al. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature 2014; 511(7507): 94-8.
[http://dx.doi.org/10.1038/nature13297] [PMID: 24847884]
[8]
Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science 1986; 232(4757): 1545-7.
[http://dx.doi.org/10.1126/science.3086977] [PMID: 3086977]
[9]
Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007; 356(15): 1517-26.
[http://dx.doi.org/10.1056/NEJMoa065213] [PMID: 17429083]
[10]
Masters SL, Dunne A, Subramanian SL, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol 2010; 11(10): 897-904.
[http://dx.doi.org/10.1038/ni.1935] [PMID: 20835230]
[11]
Jackson K, Barisone GA, Diaz E, Jin L, DeCarli C, Despa F. Amylin deposition in the brain: A second amyloid in Alzheimer disease? Ann Neurol 2013; 74(4): 517-26.
[http://dx.doi.org/10.1002/ana.23956] [PMID: 23794448]
[12]
Fawver J, Ghiwot Y, Koola C, et al. Islet amyloid polypeptide (IAPP): A second amyloid in Alzheimer’s disease. Curr Alzheimer Res 2014; 11(10): 928-40.
[http://dx.doi.org/10.2174/1567205011666141107124538] [PMID: 25387341]
[13]
Oskarsson ME, Paulsson JF, Schultz SW, Ingelsson M, Westermark P, Westermark GT. In vivo seeding and cross-seeding of localized amyloidosis: A molecular link between type 2 diabetes and Alzheimer disease. Am J Pathol 2015; 185(3): 834-46.
[http://dx.doi.org/10.1016/j.ajpath.2014.11.016] [PMID: 25700985]
[14]
Verma N, Ly H, Liu M, et al. Intraneuronal amylin deposition, peroxidative membrane injury and increased IL-1β synthesis in brains of Alzheimer’s disease patients with type-2 diabetes and in diabetic HIP rats. J Alzheimers Dis 2016; 53(1): 259-72.
[http://dx.doi.org/10.3233/JAD-160047] [PMID: 27163815]
[15]
Schultz N, Byman E, Fex M, Wennström M. Amylin alters human brain pericyte viability and NG2 expression. J Cereb Blood Flow Metab 2017; 37(4): 1470-82.
[http://dx.doi.org/10.1177/0271678X16657093] [PMID: 27354094]
[16]
Ly H, Verma N, Wu F, et al. Brain microvascular injury and white matter disease provoked by diabetes-associated hyperamylinemia. Ann Neurol 2017; 82(2): 208-22.
[http://dx.doi.org/10.1002/ana.24992] [PMID: 28696548]
[17]
Schultz N, Byman E, Wennström M, Wennström M. Levels of retinal IAPP are altered in Alzheimer’s disease patients and correlate with vascular changes and hippocampal IAPP levels. Neurobiol Aging 2018; 69: 94-101.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.05.003] [PMID: 29864717]
[18]
Martinez-Valbuena I, Valenti-Azcarate R, Amat-Villegas I, et al. Amylin as a potential link between type 2 diabetes and alzheimer disease. Ann Neurol 2019; 86(4): 539-51.
[http://dx.doi.org/10.1002/ana.25570] [PMID: 31376172]
[19]
Ly H, Verma N, Sharma S, et al. The association of circulating amylin with β‐amyloid in familial Alzheimer’s disease. Alzheimers Dement 2021; 7(1): e12130.
[http://dx.doi.org/10.1002/trc2.12130] [PMID: 33521236]
[20]
Srodulski S, Sharma S, Bachstetter AB, et al. Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin. Mol Neurodegener 2014; 9(1): 30.
[http://dx.doi.org/10.1186/1750-1326-9-30] [PMID: 25149184]
[21]
Verma N, Liu M, Ly H, et al. Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries. Kidney Int 2020; 97(1): 143-55.
[http://dx.doi.org/10.1016/j.kint.2019.07.028] [PMID: 31739987]
[22]
Ilaiwy A, Liu M, Parry TL, et al. Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo. Metabolomics 2016; 12(5): 95.
[http://dx.doi.org/10.1007/s11306-016-1022-9] [PMID: 28775675]
[23]
Royall DR, Palmer RF. Blood-based protein mediators of senility with replications across biofluids and cohorts. Brain Commun 2020; 2(1): fcz036.
[http://dx.doi.org/10.1093/braincomms/fcz036] [PMID: 32954311]
[24]
Roostaei T, Nazeri A, Felsky D, et al. Genome-wide interaction study of brain beta-amyloid burden and cognitive impairment in Alzheimer’s disease. Mol Psychiatry 2017; 22(2): 287-95.
[http://dx.doi.org/10.1038/mp.2016.35] [PMID: 27021820]
[25]
Wagner T, Page J, Burniston M, et al. Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: More than hearts and minds. Eur J Nucl Med Mol Imaging 2018; 45(7): 1129-38.
[http://dx.doi.org/10.1007/s00259-018-3995-2] [PMID: 29651545]
[26]
Castle AL, Kuo CH, Han DH, Ivy JL. Amylin-mediated inhibition of insulin-stimulated glucose transport in skeletal muscle. Am J Physiol 1998; 275(3): E531-6.
[PMID: 9725822]
[27]
Leighton B, Cooper GJS. Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature 1988; 335(6191): 632-5.
[http://dx.doi.org/10.1038/335632a0] [PMID: 3050530]
[28]
Zierath JR, Galuska D, Engström A, et al. Human islet amyloid polypeptide at pharmacological levels inhibits insulin and phorbol ester-stimulated glucose transport in in vitro incubated human muscle strips. Diabetologia 1992; 35(1): 26-31.
[http://dx.doi.org/10.1007/BF00400848] [PMID: 1541378]
[29]
Venkatanarayan A, Raulji P, Norton W, et al. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature 2015; 517(7536): 626-30.
[http://dx.doi.org/10.1038/nature13910] [PMID: 25409149]

Rights & Permissions Print Cite
Article Metrics
38
2
© 2024 Bentham Science Publishers | Privacy Policy