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

Abstract

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.

Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients

“…The higher VSV titer means a lower level of innate immunity. More severe patients were characterized with a lower level of innate immunity [ 27 ]. We also showed as a potential therapeutic the oral administration of proline-rich polypeptide complex (PRP) isolated from bovine colostrum, a nutraceutical intended to boost an immune system by increasing an innate immune response in AD patients [ 27 ].…”

“…More severe patients were characterized with a lower level of innate immunity [ 27 ]. We also showed as a potential therapeutic the oral administration of proline-rich polypeptide complex (PRP) isolated from bovine colostrum, a nutraceutical intended to boost an immune system by increasing an innate immune response in AD patients [ 27 ]. Here, we present for a first time the strong immune-enhancement activity of natural, herbal preparation, EGb, in an ex vivo model of PBLs from AD patients.…”

Effect of Strain Rate on Single Tau, Dimerized Tau and Tau-Microtubule Interface: A Molecular Dynamics Simulation Study

“…As tau protein contains a proline-rich region, it is highly relevant to study its characteristics and assesses its behavior from a neurodegenerative disease perspective. The importance of such proline-rich proteins has been evident in separate neurodegenerative disorder studies [ 83 , 84 ]. These proteins are heavily implicated in neurodegenerative diseases and traumatic brain injury, in which tau is also involved.…”

Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease

“…Colostrinin is a polypeptide affluent in proline, it is derived from ovine colostrum. It has been demonstrated to inhibit the Aβ aggregation by modulating an innate immune response [ 76 ]. Szaniszlo et al, highlighted its clinical potential in AD therapy [ 77 ].…”