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抗菌肽在阿尔茨海默病发病机制中的作用:对诊断和治疗的启示

Antimicrobial Peptides (AMPs) in the Pathogenesis of Alzheimer's Disease: Implications for Diagnosis and Treatment.

作者信息

Bruno Francesco, Malvaso Antonio, Canterini Sonia, Bruni Amalia Cecilia

机构信息

Regional Neurogenetic Centre (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy.

Association for Neurogenetic Research (ARN), 88046 Lamezia Terme, Italy.

出版信息

Antibiotics (Basel). 2022 May 28;11(6):726. doi: 10.3390/antibiotics11060726.

Abstract

Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD)-whose causes are not completely understood-and familial (FAD)-with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Aβ) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of antimicrobial peptides (AMPs) in this pathology. The literature also demonstrates that Aβ can be considered itself as an AMP; thus, representing a type of innate immune defense peptide that protects the host against a variety of pathogens. Beyond Aβ, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1, and statherin have been shown to be involved in AD. Here, we summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.

摘要

阿尔茨海默病(AD)是老年人中最常见的痴呆类型。该疾病有两种主要形式:散发性(SAD)——其病因尚未完全明确——和家族性(FAD)——具有明确的常染色体显性遗传。AD的两个主要特征是细胞外β淀粉样蛋白(Aβ)肽沉积和细胞内tau蛋白高磷酸化形式(P-tau)沉积。越来越多的研究支持散发性AD的感染假说。事实上,已有文献记载,某些病原体,如疱疹病毒和某些细菌种类,在AD患者中普遍存在,这促使近期的临床研究聚焦于该病理学中抗菌肽(AMP)的特性。文献还表明,Aβ本身可被视为一种AMP;因此,它代表了一种先天性免疫防御肽,可保护宿主抵御多种病原体。除了Aβ,其他具有抗菌活性的蛋白质,如乳铁蛋白、防御素、胱抑素、胸腺素β4、LL37、组蛋白1和statherin,也已被证明与AD有关。在此,我们总结并讨论了这些发现,并探讨了AMP在AD中的诊断和治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06e/9220182/c372e3ffa196/antibiotics-11-00726-g001.jpg

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