Elucidating mechanism of drug induced toxicity who is zach braff dating

Genome-wide identification of the mechanism of action (Mo A) of small-molecule compounds characterizing their targets, effectors, and activity modulators represents a highly relevant yet elusive goal, with critical implications for assessment of compound efficacy and toxicity.Current approaches are labor intensive and mostly limited to elucidating high-affinity binding target proteins.

However, hepatotoxicity is one of the most deleterious side effects associated with these medications.We introduce a regulatory network-based approach that elucidates genome-wide Mo A proteins based on the assessment of the global dysregulation of their molecular interactions following compound perturbation.Analysis of cellular perturbation profiles identified established Mo A proteins for 70% of the tested compounds and elucidated novel proteins that were experimentally validated.These ‘off-target’ pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA.The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical ‘weight loss’ agent.The accumulation of amyloid beta peptide (Abeta) is believed to be an early and critical event leading to synapse and neuronal cell loss in Alzheimer's Disease (AD).


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