Therapeutic Targeting of Casein Kinase 1Î/ϵ in an Alzheimer's Disease Mouse Model

Adler, Paula, Mayne, Janice, Walker, Krystal, Ning, Zhibin and Figeys, Daniel (2019) Therapeutic Targeting of Casein Kinase 1Î/ϵ in an Alzheimer's Disease Mouse Model. Journal of Proteome Research, 18 (9). pp. 3383-3393. ISSN 1535-3893

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Abstract

Sleep disturbances and memory impairment are common symptoms of Alzheimer's disease (AD). Given that the circadian clock regulates sleep, hippocampal function, and neurodegeneration, it represents a therapeutic target against AD. Casein kinase 1δ/ϵ (CK1δ/ϵ) are clock regulators and overexpressed in AD brains, making them viable targets to improve sleep and cognition. In this study, we evaluated the therapeutic potential of a small molecule CK1δ/ϵ inhibitor (PF-670462) in a triple transgenic mouse model of AD (3xTg-AD). Mass spectrometry-based proteomic analyses revealed that PF-670462 administration in 3xTg-AD mice reversed hippocampal proteomic alterations in several AD-related and clock-regulated pathways, including synaptic plasticity and amyloid precursor protein processing. Furthermore, PF-670462 administration rescued working memory deficits and normalized behavioral circadian rhythm disturbances in 3xTg-AD mice. Our study provides in vivo proof of concept for CK1δ/ϵ inhibition against AD-associated hippocampal proteomic changes, memory impairment, and circadian disturbances.

Item Type:	Article
Additional Information:	Publisher Copyright: © 2019 American Chemical Society.
Uncontrolled Keywords:	3xtg-ad,alzheimer's disease,casein kinase 1,circadian,hippocampus,mass spectrometry,memory,proteome,chemistry(all),biochemistry ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	26 Mar 2026 08:30
Last Modified:	29 Mar 2026 06:35
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102586
DOI:	10.1021/acs.jproteome.9b00312

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