| First Author | Adler P | Year | 2019 |
| Journal | J Proteome Res | Volume | 18 |
| Issue | 9 | Pages | 3383-3393 |
| PubMed ID | 31334659 | Mgi Jnum | J:294124 |
| Mgi Id | MGI:6453383 | Doi | 10.1021/acs.jproteome.9b00312 |
| Citation | Adler P, et al. (2019) Therapeutic Targeting of Casein Kinase 1delta/epsilon in an Alzheimer's Disease Mouse Model. J Proteome Res 18(9):3383-3393 |
| abstractText | 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 1delta/epsilon (CK1delta/epsilon) 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 CK1delta/epsilon 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 CK1delta/epsilon inhibition against AD-associated hippocampal proteomic changes, memory impairment, and circadian disturbances. |
