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Advanced Neurology

REVIEW ARTICLE
Bruton’s tyrosine kinase inhibitors in brain

diseases

1
Hongying Hao , Qiang Liu , and Han Jin *
2
1
1 Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, Tianjin
Medical University General Hospital, Tianjin, China
2 Central Laboratory, Tianjin Medical University General Hospital, Tianjin, China

Abstract

Bruton’s tyrosine kinase (BTK) is a non-receptor-bound intracellular signaling protein.
It is well known for its importance in the growth and malignancy of B cells, but recent
studies suggested that the BTK is also associated with many other innate immune
cells. As reported, a comparatively high level of BTK expression can be observed in
monocytes, neutrophils, macrophages, and even central nervous system-resident
immune cells like microglia. This suggests that BTK activation occurs in various acute
and chronic inflammatory conditions. Here, we discuss how BTK inhibitors might be
used to treat certain conditions, concentrating on ischemic stroke, multiple sclerosis,
neuromyelitis optica spectrum disorders, and Alzheimer’s disease. We specifically
show the significance of targeting B cells in controlling the inflammatory component
of the disease in multiple sclerosis treatment. In addition, we draw attention to the
role of BTK in the NLRP3 inflammasome activation, which is essential for brain damage
and neuroinflammation. In summary, we conclude that therapeutic targeting of BTK
in brain diseases is a potential strategy that can complement the existing therapies.
*Corresponding author:
Han Jin Keywords: Bruton’s tyrosine kinase; Brain; Inflammation; Central nervous system
(hanjin@tmu.edu.cn)
Citation: Hao H, Liu Q, Jin H.
Bruton’s tyrosine kinase inhibitors
in brain diseases. Adv Neuro. 1. Introduction
2024;3(1):2184.
https://doi.org/10.36922/an.2184 Bruton’s tyrosine kinase (BTK) belongs to the family of tyrosine kinases known as TEC
Received: November 06, 2023 (tyrosine kinase expressed in hepatocellular carcinoma). The pleckstrin homology (PH)
Accepted: January 10, 2023 domain at the N terminus, the proline-rich Tec homology, Src homology 3 (SH3), Src
homology 2, and the catalytic domain are all present in the structure of BTK (Figure 1).
Published Online: March 8, 2024 BTK was first known as genetically responsible for X-linked agammaglobulinemia,
1
Copyright: © 2024 Author(s). and was subsequently recognized for its crucial role in mediating B-cell receptor (BCR)
This is an Open-Access article signaling. In addition, BTK is involved in numerous other critical immunological
2-5
distributed under the terms of the
Creative Commons Attribution signaling pathways, including chemokine receptors, Toll-like receptors (TLR), and Fc
License, permitting distribution, receptors (FcR) signaling. Within the hematopoietic lineage, B cells, neutrophils,
6,7
and reproduction in any medium, macrophages, dendritic cells, mast cells, and hematopoietic stem cells have all been
provided the original work is
properly cited. demonstrated to express BTK. 8-10 The wide distribution of BTK and its involvement
in multiple immune signaling pathways underscore its importance in immune system
Publisher’s Note: AccScience
Publishing remains neutral with regulation and its potential as a therapeutic target in various immune-related conditions.
regard to jurisdictional claims in
published maps and institutional Not surprisingly, BTK is expressed in brain immune cells including microglia,
affiliations. which are present in the central nervous system (CNS). 11,12 Microglia are phagocytes

Volume 3 Issue 1 (2024) 1 https://doi.org/10.36922/an.2184