Multi-scale predictive modeling discovers Ibudilast as a polypharmacological agent to improve hippocampal-dependent spatial learning and memory and mitigate plaque and tangle pathology in a transgenic rat model of Alzheimer’s disease
Abstract:Alzheimer's disease (AD) is a multifactorial disease that exhibits cognitive deficits, neuronal loss, amyloid plaques, neurofibrillary tangles and neuroinflammation in the brain. We developed a multi-scale predictive modeling strategy that integrates machine learning with biophysics and systems pharmacology to model drug actions from molecular interactions to phenotypic responses. We predicted that ibudilast (IBU), a phosphodiesterase inhibitor and toll-like receptor 4 (TLR4) antagonist, inhibited multiple kin… Show more
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