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HIV-1 Impairment via UBE3A and HIV-1 Nef Interactions Utilizing the Ubiquitin Proteasome System
Study examines the interaction between a key pathogenic HIV-1 viral protein, Nef, and ubiquitin (Ub)-protein ligase E3A (UBE3A).
Date:
November 27, 2019
Creator:
Pyeon, Dohun; Rojas, Vivian K.; Price, Lenore; Kim, Seongcheol; Singh, Meharvan & Park, In-Woo
System:
The UNT Digital Library
A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy
This article gives an overview of the discovery of small-molecule bioprecursor prodrugs carrying the para-quinol scaffold on the steroidal A-ring that are preferentially metabolized in the CNS to the corresponding estrogens. Selected examples are shown to illustrate that, independently of the route of administrations and duration of treatments, these agents produce high concentration of estrogens only in the CNS without peripheral hormonal liability. 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) has been the best-studied representative of this novel type of prodrugs for brain and retina health. Specific applications in preclinical animal models of centrally-regulated and estrogen-responsive human diseases, including neurodegeneration, menopausal symptoms, cognitive decline and depression, are discussed to demonstrate the translational potential of their prodrug approach for CNS-selective and gender-independent estrogen therapy with inherent therapeutic safety.
Date:
November 19, 2019
Creator:
Prokai-Tatrai, Katalin & Prókai, László, 1958-
System:
The UNT Digital Library