New therapeutic targeting of Alzheimer's disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
New therapeutic targeting of Alzheimer's disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
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DOI：
10.1186/s12974-019-1520-6
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发表时间：
2019-07-05
影响因子：
9.3
通讯作者：
Leszek, Jerzy
中科院分区：
文献类型：
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作者：
Sochocka, Marta;Ochnik, Michal;Leszek, Jerzy
背景阿尔茨海默病(AD)目前缺乏有效的治疗方法，其主要原因是对AD病因的认识不完全。神经炎症已成为AD病理的重要组成部分，大量的实验和临床数据表明，先天免疫系统的激活在疾病的进展和症状的发展中起着至关重要的作用。方法对不同疾病严重程度的AD患者进行临床检查，并检测两种天然免疫反应，即外周血白细胞(PBL)对病毒感染(水泡性口炎病毒，VSV)的体外抵抗力，以及细胞因子：TNF-α，IFN-γ，IL-1β，IL-10，用酶联免疫吸附试验(ELISA)检测产生的细胞因子，在这项初步研究中，在口服膳食补充剂富含脯氨酸多肽复合体(PRP)(每天120毫克)治疗4周之前和之后进行了调查。结果发现AD患者先天免疫应答存在缺陷。首次证实外周血淋巴细胞对VSV感染的抵抗程度与AD的临床严重程度密切相关。我们的研究显示，细胞因子的产生存在显着差异，这表明AD患者的先天免疫机制受损。给我们的患者应用PRP可提高PBL的天然免疫反应，减少促炎和抗炎细胞因子的产生，从而抑制过度发展的炎症反应，特别是在AD严重程度较高的患者。PRP没有表现出促增殖活性。结论上述研究结果对AD患者的免疫调节治疗具有重要意义，提示PRP可能成为治疗AD等神经炎性疾病的潜在靶点。
BackgroundThe lack of effective treatment for Alzheimer's disease (AD) stems mainly from the incomplete understanding of AD causes. Neuroinflammation has emerged as an important component of AD pathology, and a vast number of experimental and clinical data indicated a crucial role for the activation of the innate immune system in disease promotion and symptom progression.MethodsClinical examinations of AD patients in a different stage of disease severity in correlation with the measurement of two innate immune reactions, i.e., peripheral blood leukocyte (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo, and cytokines: TNF-alpha, IFN-gamma, IL-1 beta, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 mu g of PRP/day). The potential effect of PRP on the distribution of PBLs' subpopulations has been specified.ResultsWe have found a deficiency in innate immune response in AD patients. It was demonstrated for the first time that the degree of PBLs resistance to VSV infection was closely related to the stage of clinical severity of AD. Our study showed significant differences in cytokine production which pointed that in AD patients innate immune mechanisms are impaired. Administration of PRP to our patients increased innate immune response of PBLs and declined pro- and anti-inflammatory cytokine production, thus subduing the excessively developed inflammatory response, especially among patients with high severity of AD. PRP did not exhibit a pro-proliferative activity. It was showed, however, significant influence of PRP on the distribution of PBLs' subpopulations.ConclusionThe findings mentioned above might be crucial in the context of potential application of immunomodulatory therapy in AD patients and indicated PRP as a potential target for future treatments in neuroinflammatory diseases like AD.