Old age-associated phenotypic screening for Alzheimer's disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa.
Alzheimer's disease (AD) is the most frequent age-associated dementia with no treatments that can prevent or slow its progression. Since age is by far the major risk factor for AD, there is a strong rationale for an alternative approach to drug discovery based upon the biology of aging. Phenotypic screening assays that reflect multiple, age-associated neurotoxicity pathways rather than single molecular targets can identify compounds that have therapeutic efficacy by targeting aspects of aging that contribute to AD pathology. And, while the suitability of any single assay can be questioned, a combination of assays can make reliable predictions about the neuroprotective effects of compounds in vivo. Therefore, our lab has developed a combination of phenotypic screening assays that are ideally suited not only to identify novel neuroprotective compounds for the treatment of AD but also their target pathways, thereby potentially providing new therapeutic targets for disease treatment. Using these assays, we screened a large library of extracts from plants with identified pharmacological uses. Analysis of one of these extracts from the plant Yerba santa (Eriodictyon californicum) identified the flavanone sterubin as the active component and further studies showed it to be a potent neuroprotective and anti-inflammatory compound.
['Fischer|Wolfgang|W|', 'Currais|Antonio|A|', 'Liang|Zhibin|Z|', 'Pinto|Antonio|A|', 'Maher|Pamela|P|']
D000818:Animals D002851:Chromatography, High Pressure Liquid D004353:Drug Evaluation, Preclinical D031322:Eriodictyon D006801:Humans D013058:Mass Spectrometry D051379:Mice D000066829:Neuroprotection D018696:Neuroprotective Agents D016716:PC12 Cells D010641:Phenotype D010936:Plant Extracts D051381:Rats D017382:Reactive Oxygen Species D015203:Reproducibility of Results
ATF4 Ferroptosis Glutathione Inflammation Nrf2 Oxidative stress