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Review

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

1
Institute of Biochemistry, Molecular Cell Biology, University Clinic Hamburg-Eppendorf, 20251 Hamburg, Germany
2
PM Research Center, 20 Kaggeholm, Ekerö, 178 54 Stockholm, Sweden
3
Victor Babes National Institute of Pathology, 050096 București, Romania
4
Bevill Biomedical Sciences Research Building, UAB Birmingham, AL 35294-2170, USA
5
Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, ul. Postepu 36A, Jastrzębiec, 05-552 Magdalenka, Poland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(9), 880; https://doi.org/10.3390/pharmaceutics12090880
Received: 7 August 2020 / Revised: 7 September 2020 / Accepted: 14 September 2020 / Published: 16 September 2020
(This article belongs to the Special Issue New Drug Delivery across the Blood–Brain Barrier)
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. View Full-Text
Keywords: Alzheimer; blood brain barrier; CD4+ T cells; migration; Th17 Alzheimer; blood brain barrier; CD4+ T cells; migration; Th17
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MDPI and ACS Style

Kubick, N.; Flournoy, P.C.H.; Enciu, A.-M.; Manda, G.; Mickael, M.-E. Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease. Pharmaceutics 2020, 12, 880. https://doi.org/10.3390/pharmaceutics12090880

AMA Style

Kubick N, Flournoy PCH, Enciu A-M, Manda G, Mickael M-E. Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease. Pharmaceutics. 2020; 12(9):880. https://doi.org/10.3390/pharmaceutics12090880

Chicago/Turabian Style

Kubick, Norwin, Patrick C.H. Flournoy, Ana-Maria Enciu, Gina Manda, and Michel-Edwar Mickael. 2020. "Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease" Pharmaceutics 12, no. 9: 880. https://doi.org/10.3390/pharmaceutics12090880

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