Home
Resources
Publications
Inhibition of Casein Kinase 1δ/εimproves Cognitive-Affective Behavior and Reduces Amyloid Load in the APP-PS1 Mouse Model of Alzheimer's Disease

Inhibition of Casein Kinase 1δ/εimproves Cognitive-Affective Behavior and Reduces Amyloid Load in the APP-PS1 Mouse Model of Alzheimer's Disease

S Sundaram, S Nagaraj, H Mahoney, A Portugues, W Li, K Millsaps, J Faulkner, A Yunus, C Burns, C Bloom, M Said, L Pinto, S Azam, M Flores, A Henriksen, J Gamsby, D Gulick

Sci Rep. 2019 Sep 24;9(1):13743.

PMID: 31551449

Abstract:

Circadian rhythm disruption is one of the earliest biomarkers of Alzheimer's disease (AD), and there exists a bidirectional relationship by which dysfunctions in the circadian clock drive AD pathology and AD pathology drives circadian dysfunction. Casein kinase 1 (CK1) isoforms ε and δ, key circadian regulators, are significantly upregulated in AD and may contribute to AD pathogenesis. In the current studies, we have examined how inhibition of CK1ε/δ with PF-670462 (at 10 mg/kg, δ isoform selective, or 30 mg/kg, δ and ε selective) impacts regional Aβ and circadian gene expression in 10-13 month old APP-PS1 mice and nontransgenic controls. We have also assessed circadian, cognitive, and affective behavioral correlates of these neural changes. At baseline, APP-PS1 mice showed a short period, as well as impaired cognitive performance in both prefrontal cortex and hippocampus-dependent tasks. Both doses of PF-670462 lengthened the period and improved affect, whereas only the higher dose improved cognition. Further, PF-670462 treatment produced a dose-dependent reduction in amyloid burden - overall Aβ signal decreased in all three areas; in the prefrontal cortex and hippocampus, PF-670462 also reduced plaque size. Together, these findings support chronotherapy as a potential tool to improve behavior in AD.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP950912808	PF-670462		950912-80-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: