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Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.
Proc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFCase report: Endolymphatic sac tumor with blurred vision.
Front Oncol
January 2025
The Second Clinical Medicine College, Jinan University, Shenzhen, China.
Introduction: Endolymphatic sac tumor (ELST) is a rare neoplasm that exhibits aggressive growth primarily in the endolymphatic capsule and can potentially affect nearby neurovascular structures. The diagnosis of ELST poses challenges due to its low prevalence, gradual progression, and nonspecific symptomatology. It is currently believed that prompt surgical intervention is recommended for endolymphatic sac tumors upon diagnosis.
View Article and Find Full Text PDFDevelopment of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan. Electronic address:
Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.
View Article and Find Full Text PDFHypoxia-Inducible Factor in Renal Cell Carcinoma: From Molecular Insights to Targeted Therapies.
Genes (Basel)
December 2024
Department of Health Science, University of Florence, 50134 Florence, Italy.
Mutations of the von Hippel-Lindau () tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes.
View Article and Find Full Text PDFRelationship between ZHX2 Expression and VHL Gene Alteration in VHL-associated and Sporadic Hemangioblastomas of the Central Nervous System.
J Kidney Cancer VHL
December 2024
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Central nervous system hemangioblastoma (CNS-HB) is the most common manifestation of von Hippel-Lindau disease (VHL). The main axis of the CNS-HB pathway is the VHL-HIF signaling pathway. Recently, we proposed an alternative VHL-JAK-STAT pathway in CNS-HB.
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