Cargando…

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

BACKGROUND: The 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 activati...

Descripción completa

Detalles Bibliográficos
Autores principales: Sochocka, Marta, Ochnik, Michał, Sobczyński, Maciej, Siemieniec, Iwona, Orzechowska, Beata, Naporowski, Piotr, Leszek, Jerzy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612126/
https://www.ncbi.nlm.nih.gov/pubmed/31277647
http://dx.doi.org/10.1186/s12974-019-1520-6
_version_ 1783432829174022144
author Sochocka, Marta
Ochnik, Michał
Sobczyński, Maciej
Siemieniec, Iwona
Orzechowska, Beata
Naporowski, Piotr
Leszek, Jerzy
author_facet Sochocka, Marta
Ochnik, Michał
Sobczyński, Maciej
Siemieniec, Iwona
Orzechowska, Beata
Naporowski, Piotr
Leszek, Jerzy
author_sort Sochocka, Marta
collection PubMed
description BACKGROUND: The 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. METHODS: Clinical 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-α, IFN-γ, IL-1β, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 μg of PRP/day). The potential effect of PRP on the distribution of PBLs’ subpopulations has been specified. RESULTS: We 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. CONCLUSION: The 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1520-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6612126
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-66121262019-07-16 New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study Sochocka, Marta Ochnik, Michał Sobczyński, Maciej Siemieniec, Iwona Orzechowska, Beata Naporowski, Piotr Leszek, Jerzy J Neuroinflammation Research BACKGROUND: The 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. METHODS: Clinical 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-α, IFN-γ, IL-1β, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 μg of PRP/day). The potential effect of PRP on the distribution of PBLs’ subpopulations has been specified. RESULTS: We 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. CONCLUSION: The 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1520-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-05 /pmc/articles/PMC6612126/ /pubmed/31277647 http://dx.doi.org/10.1186/s12974-019-1520-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sochocka, Marta
Ochnik, Michał
Sobczyński, Maciej
Siemieniec, Iwona
Orzechowska, Beata
Naporowski, Piotr
Leszek, Jerzy
New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title_full New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title_fullStr New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title_full_unstemmed New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title_short New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
title_sort new therapeutic targeting of alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612126/
https://www.ncbi.nlm.nih.gov/pubmed/31277647
http://dx.doi.org/10.1186/s12974-019-1520-6
work_keys_str_mv AT sochockamarta newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT ochnikmichał newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT sobczynskimaciej newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT siemienieciwona newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT orzechowskabeata newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT naporowskipiotr newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy
AT leszekjerzy newtherapeutictargetingofalzheimersdiseasewiththepotentialuseofprolinerichpolypeptidecomplextomodulateaninnateimmuneresponsepreliminarystudy