Rational Design, Optimization and Synthesis of Indole-based Small Molecules Targeting Alzheimer’s disease

Summary

Alzheimer’s disease (AD) is a neurodegenerative brain disorder that has an increasingly large burden on health and social care systems. The pathophysiology involves the accumulation of extracellular amyloid-beta plaques (Aβ) and intracellular neurofibrillary tangles contributing to neuronal death and leading to cognition impairment.

 Several attempts have been made to treat AD, while most of them end in failure. However, with the deepening study of pathogenesis of AD, the expression of HDAC6 in the hippocampus, which plays a major role of the memory formation, is becoming worth of notice. Overall, the significantly increased expression of HDAC6 in brain regions is deleterious to neuron survival in AD patients. Based on these findings, the inhibition of HDAC6 seems to be a potential therapeutic method for the treatment of AD. Our research objective is to design and synthesize Novel HDAC6 Inhibitors with promising activity on AD based on profound literature survey and SAR studies.

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