The Hippo signaling pathway as a therapeutic target in Alzheimer's disease

Doris Chen; Stella Wigglesworth-Littlewood; Frank J Gunn-Moore

doi:10.1186/s13024-025-00891-4

The Hippo signaling pathway as a therapeutic target in Alzheimer's disease

Doris Chen, Stella Wigglesworth-Littlewood, Frank J Gunn-Moore^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The Hippo signaling pathway is well-known for its regulation of organ size, cell proliferation, apoptosis, and cell migration and differentiation. Recent studies have demonstrated that Hippo signaling also plays important roles in the nervous system, being involved in neuroinflammation, neuronal differentiation, and neuronal death and degeneration. As such, dysregulation of Hippo signaling, particularly of its core kinases MST1/2 and LATS1/2, has begun to attract attention in the Alzheimer’s disease (AD) field. Here, we discuss the therapeutic potential of targeting the Hippo pathway in AD by providing an overview of Hippo signaling with regards to its function in the nervous system, evidence for its dysregulation in AD patients and models, and recent studies involving genetic or pharmacological modulation of this pathway in AD.

Original language	English
Article number	100
Pages (from-to)	1-31
Number of pages	31
Journal	Molecular Neurodegeneration
Volume	20
DOIs	https://doi.org/10.1186/s13024-025-00891-4
Publication status	Published - 26 Sept 2025

Access to Document

10.1186/s13024-025-00891-4Licence: CC BY

Chen-et-al-2025-The-Hippo-signaling-pathway-MolNeurodegeneration-20-100-CCBY
Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 5.48 MBLicence: CC BY

Cite this

@article{31311fb9497e4246b77001326a1940ba,

title = "The Hippo signaling pathway as a therapeutic target in Alzheimer's disease",

abstract = "The Hippo signaling pathway is well-known for its regulation of organ size, cell proliferation, apoptosis, and cell migration and differentiation. Recent studies have demonstrated that Hippo signaling also plays important roles in the nervous system, being involved in neuroinflammation, neuronal differentiation, and neuronal death and degeneration. As such, dysregulation of Hippo signaling, particularly of its core kinases MST1/2 and LATS1/2, has begun to attract attention in the Alzheimer{\textquoteright}s disease (AD) field. Here, we discuss the therapeutic potential of targeting the Hippo pathway in AD by providing an overview of Hippo signaling with regards to its function in the nervous system, evidence for its dysregulation in AD patients and models, and recent studies involving genetic or pharmacological modulation of this pathway in AD.",

author = "Doris Chen and Stella Wigglesworth-Littlewood and Gunn-Moore, {Frank J}",

note = "Funding: This research was funded by Alzheimer{\textquoteright}s Research UK, the Alzheimer{\textquoteright}s Society, the RS Macdonald Charitable Trust, and the University of St Andrews.",

year = "2025",

month = sep,

day = "26",

doi = "10.1186/s13024-025-00891-4",

language = "English",

volume = "20",

pages = "1--31",

journal = "Molecular Neurodegeneration",

issn = "1750-1326",

publisher = "Springer Nature",

}

TY - JOUR

T1 - The Hippo signaling pathway as a therapeutic target in Alzheimer's disease

AU - Chen, Doris

AU - Wigglesworth-Littlewood, Stella

AU - Gunn-Moore, Frank J

N1 - Funding: This research was funded by Alzheimer’s Research UK, the Alzheimer’s Society, the RS Macdonald Charitable Trust, and the University of St Andrews.

PY - 2025/9/26

Y1 - 2025/9/26

N2 - The Hippo signaling pathway is well-known for its regulation of organ size, cell proliferation, apoptosis, and cell migration and differentiation. Recent studies have demonstrated that Hippo signaling also plays important roles in the nervous system, being involved in neuroinflammation, neuronal differentiation, and neuronal death and degeneration. As such, dysregulation of Hippo signaling, particularly of its core kinases MST1/2 and LATS1/2, has begun to attract attention in the Alzheimer’s disease (AD) field. Here, we discuss the therapeutic potential of targeting the Hippo pathway in AD by providing an overview of Hippo signaling with regards to its function in the nervous system, evidence for its dysregulation in AD patients and models, and recent studies involving genetic or pharmacological modulation of this pathway in AD.

AB - The Hippo signaling pathway is well-known for its regulation of organ size, cell proliferation, apoptosis, and cell migration and differentiation. Recent studies have demonstrated that Hippo signaling also plays important roles in the nervous system, being involved in neuroinflammation, neuronal differentiation, and neuronal death and degeneration. As such, dysregulation of Hippo signaling, particularly of its core kinases MST1/2 and LATS1/2, has begun to attract attention in the Alzheimer’s disease (AD) field. Here, we discuss the therapeutic potential of targeting the Hippo pathway in AD by providing an overview of Hippo signaling with regards to its function in the nervous system, evidence for its dysregulation in AD patients and models, and recent studies involving genetic or pharmacological modulation of this pathway in AD.

U2 - 10.1186/s13024-025-00891-4

DO - 10.1186/s13024-025-00891-4

M3 - Article

SN - 1750-1326

VL - 20

SP - 1

EP - 31

JO - Molecular Neurodegeneration

JF - Molecular Neurodegeneration

M1 - 100

ER -

The Hippo signaling pathway as a therapeutic target in Alzheimer's disease

Abstract

Access to Document

Fingerprint

Cite this