Limiting RyR2 Open Time Prevents Alzheimer’s Disease-Related Neuronal Hyperactivity and Memory Loss but Not β-Amyloid Accumulation
Jinjing Yao, Bo Sun, Ádám Institóris, Xiaoqin Zhan, Wenting Guo, Zhenpeng Song, Yajing Liu, Florian Hiess, Andrew K. J. Boyce, Mingke Ni, Ruiwu Wang, Henk ter Keurs, Thomas G. Back, Michael Fill, Roger Thompson, Ray W. Turner, Grant R. Gordon, S.R. Wayne Chen
Abstract
current, a well-known neuronal excitability control that is downregulated in AD. Pharmacologically limiting RyR2 open time with the R-carvedilol enantiomer (but not racemic carvedilol) prevents and rescues neuronal hyperactivity, memory impairment, and neuron loss even in late stages of AD. These AD-related deficits are prevented even with continued β-amyloid accumulation. Thus, limiting RyR2 open time may be a hyperactivity-directed, non-β-amyloid-targeted anti-AD strategy.
Topics & Concepts
NeuroscienceRyanodine receptor 2Hippocampal formationAlzheimer's diseaseMemory impairmentAmyloid (mycology)MedicineBiologyRyanodine receptorInternal medicineDiseaseReceptorPathologyCognitionNeuroscience and Neuropharmacology ResearchAlzheimer's disease research and treatmentsCholinesterase and Neurodegenerative Diseases