GSK356278 / GSK - LARVOL DELTA

Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice. (PubMed, Alzheimers Dement) - "Early episodic memory deficits in AD linked to oAβ-induced synaptic dysfunction. Isoproterenol and GSK356278 improve mossy fiber-LTP and fear memory deficits. FLIM-FRET shows treatments restore cAMP signaling in dentate gyrus neurons. Isoproterenol reduces synapsin I hyperphosphorylation and microgliosis. Enhancing cAMP signaling may help mitigate early memory deficits in AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • CA3

Quantification of human brain PDE4 occupancy by GSK356278: A [(11)C](R)-rolipram PET study. (PubMed, J Cereb Blood Flow Metab) - "We present the first report of a direct estimation of PDE4 blockade in the living human brain. In vivo affinity of GSK356278 for the PDE4, estimated in this early phase study, was combined with GSK356278 safety and tolerability data to decide on a therapeutic dose for future clinical development."

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