Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Microglia PTK2B/Pyk2 in the Pathogenesis of Alzheimer’s Disease

Author(s): Yun Guo, Cheng-Kun Sun, Lian Tang and Meng-Shan Tan*

Volume 20, Issue 10, 2023

Published on: 06 February, 2024

Page: [692 - 704] Pages: 13

DOI: 10.2174/0115672050299004240129051655

Price: $65

Abstract

Alzheimer’s disease (AD) is a highly hereditary disease with complex genetic susceptibility factors. Extensive genome-wide association studies have established a distinct susceptibility link between the protein tyrosine kinase 2β (PTK2B) gene and late-onset Alzheimer’s disease (LOAD), but the specific pathogenic mechanisms remain incompletely understood. PTK2B is known to be expressed in neurons, and recent research has revealed its more important significance in microglia. Elucidating the role of PTK2B high expression in microglia in AD’s progression is crucial for uncovering novel pathogenic mechanisms of the disease. Our review of existing studies suggests a close relationship between PTK2B/proline-rich tyrosine kinase 2 (Pyk2) and tau pathology, and this process might be β-amyloid (Aβ) dependence. Pyk2 is hypothesized as a pivotal target linking Aβ and tau pathologies. Concurrently, Aβ-activated Pyk2 participates in the regulation of microglial activation and its proinflammatory functions. Consequently, it is reasonable to presume that Pyk2 in microglia contributes to amyloid-induced tau pathology in AD via a neuroinflammatory pathway. Furthermore, many things remain unclear, such as identifying the specific pathways that lead to the release of downstream inflammatory factors due to Pyk2 phosphorylation and whether all types of inflammatory factors can activate neuronal kinase pathways. Additionally, further in vivo experiments are essential to validate this hypothesized pathway. Considering PTK2B/Pyk2’s potential role in AD pathogenesis, targeting this pathway may offer innovative and promising therapeutic approaches for AD.

Keywords: PTK2B, Pyk2, Alzheimer’s disease, microglia, neuroinflammatory, amyloid, tau hyperphosphorylation.


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy