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Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease

The effect of Alzheimer’s disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proin...

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Autores principales: Kubick, Norwin, Flournoy, Patrick C. Henckell, Enciu, Ana-Maria, Manda, Gina, Mickael, Michel-Edwar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558445/
https://www.ncbi.nlm.nih.gov/pubmed/32948022
http://dx.doi.org/10.3390/pharmaceutics12090880
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author Kubick, Norwin
Flournoy, Patrick C. Henckell
Enciu, Ana-Maria
Manda, Gina
Mickael, Michel-Edwar
author_facet Kubick, Norwin
Flournoy, Patrick C. Henckell
Enciu, Ana-Maria
Manda, Gina
Mickael, Michel-Edwar
author_sort Kubick, Norwin
collection PubMed
description The effect of Alzheimer’s disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proinflammatory cytokines that reduce endothelial integrity and stimulate astrocytes, resulting in the production of amyloid β. Anti-inflammatory subpopulations such as Th2 and Tregs reduce inflammation and regulate the function of Th1 and Th17. Recently, pathogenic Th17 has been shown to have a superior infiltrating capacity compared to other major CD4+ T cell subpopulations. Alzheimer’s drugs such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) are known to play an important part in regulating the mechanisms of the neurotransmitters. However, little is known about the effect of these drugs on CD4+ T cell subpopulations’ infiltration of the brain during AD. In this review, we focus on understanding the influence of AD drugs on CD4+ T cell subpopulation interactions with the BBB in AD. While current AD therapies improve endothelial integrity and reduce astrocytes activations, they vary according to their influence on various CD4+ T cell subpopulations. Donepezil reduces the numbers of Th1 but not Th2, Rivastigmine inhibits Th1 and Th17 but not Th2, and memantine reduces Th1 but not Treg. However, none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis. Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis.
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spelling pubmed-75584452020-10-26 Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease Kubick, Norwin Flournoy, Patrick C. Henckell Enciu, Ana-Maria Manda, Gina Mickael, Michel-Edwar Pharmaceutics Review The effect of Alzheimer’s disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proinflammatory cytokines that reduce endothelial integrity and stimulate astrocytes, resulting in the production of amyloid β. Anti-inflammatory subpopulations such as Th2 and Tregs reduce inflammation and regulate the function of Th1 and Th17. Recently, pathogenic Th17 has been shown to have a superior infiltrating capacity compared to other major CD4+ T cell subpopulations. Alzheimer’s drugs such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) are known to play an important part in regulating the mechanisms of the neurotransmitters. However, little is known about the effect of these drugs on CD4+ T cell subpopulations’ infiltration of the brain during AD. In this review, we focus on understanding the influence of AD drugs on CD4+ T cell subpopulation interactions with the BBB in AD. While current AD therapies improve endothelial integrity and reduce astrocytes activations, they vary according to their influence on various CD4+ T cell subpopulations. Donepezil reduces the numbers of Th1 but not Th2, Rivastigmine inhibits Th1 and Th17 but not Th2, and memantine reduces Th1 but not Treg. However, none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis. Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis. MDPI 2020-09-16 /pmc/articles/PMC7558445/ /pubmed/32948022 http://dx.doi.org/10.3390/pharmaceutics12090880 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kubick, Norwin
Flournoy, Patrick C. Henckell
Enciu, Ana-Maria
Manda, Gina
Mickael, Michel-Edwar
Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title_full Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title_fullStr Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title_full_unstemmed Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title_short Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease
title_sort drugs modulating cd4+ t cells blood–brain barrier interaction in alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558445/
https://www.ncbi.nlm.nih.gov/pubmed/32948022
http://dx.doi.org/10.3390/pharmaceutics12090880
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