{"title":"Neu1 通过免疫系统治疗阿尔茨海默病的潜力","authors":"Aiza Khan, Sumit Das, Consolato Sergi","doi":"10.1177/1533317521996147","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.</p>","PeriodicalId":50816,"journal":{"name":"American Journal of Alzheimers Disease and Other Dementias","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624071/pdf/","citationCount":"0","resultStr":"{\"title\":\"Therapeutic Potential of Neu1 in Alzheimer's Disease Via the Immune System.\",\"authors\":\"Aiza Khan, Sumit Das, Consolato Sergi\",\"doi\":\"10.1177/1533317521996147\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Alzheimer's Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.</p>\",\"PeriodicalId\":50816,\"journal\":{\"name\":\"American Journal of Alzheimers Disease and Other Dementias\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2021-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624071/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Alzheimers Disease and Other Dementias\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/1533317521996147\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Alzheimers Disease and Other Dementias","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/1533317521996147","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
阿尔茨海默病(AD)的病理特征是可溶性低聚物的积累,导致细胞外β-淀粉样蛋白沉积,形成脑内神经窦斑块和含tau的神经元内神经纤维缠结。一种解释这些蛋白质形成的机制是,小胶质细胞/巨噬细胞的吞噬功能受损,导致β-淀粉样蛋白可溶性低聚物的清除功能缺陷,从而刺激淀粉样蛋白斑块的聚集,进而引发注意力缺失症。不过,研究表明,激活 M2 状态的巨噬细胞可减少有毒的寡聚体。NEU1基因突变与一种罕见疾病--苷酸沉着症有关。NEU1 缺乏症也可能导致类似 AD 的淀粉样蛋白生成过程。因此,NEU1 被认为具有治疗 AD 的潜力,其潜在机制是溶酶体外泌。然而,研究表明 NEU1 可激活处于 M2 状态的巨噬细胞,如前所述,M2 状态对减少毒性寡聚体至关重要。在这篇综述中,作者讨论了 NEU1 通过免疫系统对注意力缺失症的潜在治疗作用。
Therapeutic Potential of Neu1 in Alzheimer's Disease Via the Immune System.
Alzheimer's Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.
期刊介绍:
American Journal of Alzheimer''s Disease and other Dementias® (AJADD) is for professionals on the frontlines of Alzheimer''s care, dementia, and clinical depression--especially physicians, nurses, psychiatrists, administrators, and other healthcare specialists who manage patients with dementias and their families. This journal is a member of the Committee on Publication Ethics (COPE).