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ThesisJan 2024

Exploring the Transporters Dynamics in Blood-Brain Barrier Functionality and Innovative Treatments for Non-Alcoholic Fatty Liver Disease/Steatohepatitis

Zhou, X
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Abstract
The second part of the dissertation (Part B) shifts focus to the global health issue of NAFLD and its more severe form, NASH. It investigates Cis-Regulation Therapy (CRT) as a novel treatment approach, utilizing nuclease-deficient gene-editing technologies to modify gene regulatory elements for therapeutic ends. Approximately 30% of people worldwide are affected by NAFLD, and about 25% of these cases may advance to NASH. NASH represents a more serious stage of NAFLD, marked by liver inflammation and damage due to fat accumulation in the liver. About 25% of those with NAFLD progress to NASH, characterized by significant liver inflammation and damage due to fat accumulation. Currently, the pharmacological treatment options for NAFLD/NASH are severely limited. Our study investigates the potential of CRT as an innovative treatment strategy. In our research, we explored the effectiveness of CRT as a promising new treatment strategy. CRT employs nuclease-deficient gene-editing technologies, such as dead Cas9 (dCas9) combined with transcriptional modulators, to alter the activity of gene regulatory elements for therapeutic purposes. The goal of this part of the dissertation research specifically focuses on the nuclear receptor-like protein 1 (NURR1, NR4A2), a transcription factor critical in regulating inflammation which is a hallmark of NASH.
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