4.7 Article

New therapeutic targeting of Alzheimer's disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study

Journal

JOURNAL OF NEUROINFLAMMATION
Volume 16, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s12974-019-1520-6

Keywords

Impaired innate immunity; Vesicular stomatitis virus (VSV); Resistance to viral infection; Alzheimer's disease; Proline-rich polypeptide complex (PRP); Cytokine; PBLs

Funding

  1. Wroclaw Medical University (Wroclaw, Poland)
  2. Le Loch Healthcare (Warsaw, Poland) research funds

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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.

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