Format

Send to

Choose Destination
Redox Biol. 2019 Feb;21:101089. doi: 10.1016/j.redox.2018.101089. Epub 2018 Dec 21.

Old age-associated phenotypic screening for Alzheimer's disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa.

Author information

1
The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, United States.
2
The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, United States. Electronic address: pmaher@salk.edu.

Abstract

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.

KEYWORDS:

ATF4; Ferroptosis; Glutathione; Inflammation; Nrf2; Oxidative stress

PMID:
30594901
PMCID:
PMC6309122
DOI:
10.1016/j.redox.2018.101089
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center