Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prion-like protein
aggregation underlies the pathology of a group of fatal neurodegenerative diseases in humans, including Alzheimer's disease (AD), Parkinson's disease,
amyotrophic lateral sclerosis
, and transmissible spongiform encephalopathy. At present, few high-throughput screening (HTS) systems are available for anti-prion small-molecule identification. Here we describe an innovative phenotypic HTS system in yeast that allows for efficient identification of chemical compounds that eliminate the yeast prion [SWI
+
]. We show that some identified anti-[SWI
+
] compounds can destabilize other non-[SWI
+
] prions, and their antagonizing effects can be prion- and/or variant specific. Intriguingly, among the identified hits are several previously identified anti-PrP
Sc
compounds and a couple of US Food and Drug Administration-approved drugs for AD treatment, validating the efficacy of this HTS system. Moreover, a few hits can reduce proteotoxicity induced by expression of several pathogenic mammalian proteins. Thus, we have established a useful HTS system for identifying compounds that can potentially antagonize prionization and human proteinopathies.
...
PMID:Identifying Anti-prion Chemical Compounds Using a Newly Established Yeast High-Throughput Screening System. 3166 17