Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun;33(6):2951-2962.
doi: 10.1007/s10787-025-01796-w. Epub 2025 Jun 3.

Targeting the JAK/STAT3/SOCS signaling pathway in Alzheimer's disease

Hayder M Al-Kuraishy  1 , Ghassan M Sulaiman  2 , Hamdoon A Mohammed  3 , Hebatallah M Saad  4 , Ali I Al-Gareeb  5 , Ali K Albuhadily  1
Affiliations
Review

Targeting the JAK/STAT3/SOCS signaling pathway in Alzheimer's disease

Hayder M Al-Kuraishy et al. Inflammopharmacology. 2025 Jun.

Abstract

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease worldwide. The pathogenesis of AD is related to the progressive neuronal apoptosis due to the advanced accumulation of extracellular amyloid beta (Aβ) peptide and intracellular neurofibrillary tangles (NFTs), which are caused by hyperphosphorylation of tau protein. The accumulation of Aβ and NFTs in AD is affected by diverse signaling pathways, such as Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT), which are involved in the JAK/STAT signaling pathway. This signaling pathway controls cell proliferation, differentiation, and survival. The JAK/STAT signaling pathway plays a critical role in the development of neurodegeneration and neuroinflammation in AD. Also, suppressor of cytokine signaling (SOCS), a negative regulator of the JAK/STAT signaling pathway, is also affected in AD. Nevertheless, the fundamental mechanism for the dysregulation of the JAK/STAT3/SOCS signaling pathway in AD is not completely explained. Henceforth, this review aims to explain and discuss the precise role of the JAK/STAT3/SOCS signaling pathway in AD and how targeting of this pathway could be effective in the management of AD.

Keywords: Alzheimer’s disease; Janus tyrosine kinase; Signal transducer and activator of transcription; Suppressor of cytokine signaling.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declare no conflict of interest.

Similar articles

See all similar articles

References

    1. Abubaker M, Stanton J, Mahon O, et al (2024) Amyloid Beta – induced leptomeningeal cell JAK/STAT signalling regulates inflammatory responses of astrocytes in Alzheimer’s Disease
    1. Aggarwal BB, Kunnumakkara AB, Harikumar KB et al (2009) Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci 1171:59–76 - DOI - PubMed - PMC
    1. Ali NH, Al-Kuraishy HM, Al-Gareeb AI et al (2024) New insight on the potential detrimental effect of metabolic syndrome on the Alzheimer disease neuropathology: Mechanistic role. J Cell Mol Med 28:e70118 - DOI - PubMed - PMC
    1. Al-kuraishy HM, Sulaiman GM, Mohammed HA et al (2025) Alterations in the processing of platelet APP (Amyloid beta precursor protein) in Alzheimer disease: the possible nexus. Neuropsychopharmacol Reports 45:e12525 - DOI
    1. Al-Kuraishy HM, Sulaiman GM, Mohammed HA et al (2025a) Amyloid-β and heart failure in Alzheimer’s disease: the new vistas. Front Med 12:1494101 - DOI

MeSH terms

LinkOut - more resources