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Autor(en) / Beteiligte
Titel
Small Molecule Phenotypic Screen Identifies Novel Regulators of LDLR Expression
Ist Teil von
  • ACS chemical biology, 2020-12, Vol.15 (12), p.3262-3274
Ort / Verlag
United States: American Chemical Society
Erscheinungsjahr
2020
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The current treatment options for AD are limited to ameliorating cognitive decline temporarily and not reversing or preventing the progression of dementia. Hence, more effective therapeutic strategies are needed to combat this devastating disease. The low-density lipoprotein receptor has been shown to modulate the neuronal metabolism of cholesterol and apolipoprotein E, a major genetic risk factor for AD. LDLR overexpression in mice has been shown to increase amyloid-β clearance and reduce amyloid deposition. We conducted a phenotypic screen to identify novel signaling pathways and targets that regulate LDLR expression in glial cells using an annotated compound library of approximately 29 000 compounds. The screen identified novel targets such as polo like kinase 1 (PLK1), activin receptor like kinase 5 (ALK5), and serotonin transporter (SERT). We used genetic, chemical biology and pathway analysis to confirm the target hypothesis. This work highlights that phenotypic screening is a promising strategy to identify novel mechanisms and targets for therapeutic intervention of complex neurodegenerative disorders.
Sprache
Englisch
Identifikatoren
ISSN: 1554-8929
eISSN: 1554-8937
DOI: 10.1021/acschembio.0c00851
Titel-ID: cdi_proquest_miscellaneous_2467617704
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