دورية أكاديمية
Genetic predisposition similarities between NASH and ASH: Identification of new therapeutic targets
| العنوان: | Genetic predisposition similarities between NASH and ASH: Identification of new therapeutic targets |
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| المؤلفون: | Bianco C., Casirati E., Malvestiti F., Valenti L. |
| المساهمون: | C. Bianco, E. Casirati, F. Malvestiti, L. Valenti |
| بيانات النشر: | Elsevier B.V. |
| سنة النشر: | 2021 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | alcoholic liver disease, cirrhosi, fatty liver disease, genetic, IL32, interleukin-32, MBOAT7, non-alcoholic fatty liver disease, PNPLA3, precision medicine, steatohepatiti, therapy, Settore MED/03 - Genetica Medica |
| الوصف: | Fatty liver disease can be triggered by a combination of excess alcohol, dysmetabolism and other environmental cues, which can lead to steatohepatitis and can evolve to acute/chronic liver failure and hepatocellular carcinoma, especially in the presence of shared inherited determinants. The recent identification of the genetic causes of steatohepatitis is revealing new avenues for more effective risk stratification. Discovery of the mechanisms underpinning the detrimental effect of causal mutations has led to some breakthroughs in the comprehension of the pathophysiology of steatohepatitis. Thanks to this approach, hepatocellular fat accumulation, altered lipid droplet remodelling and lipotoxicity have now taken centre stage, while the role of adiposity and gut-liver axis alterations have been independently validated. This process could ignite a virtuous research cycle that, starting from human genomics, through omics approaches, molecular genetics and disease models, may lead to the development of new therapeutics targeted to patients at higher risk. Herein, we also review how this knowledge has been applied to: a) the study of the main PNPLA3 I148M risk variant, up to the stage of the first in-human therapeutic trials; b) highlight a role of MBOAT7 downregulation and lysophosphatidyl-inositol in steatohepatitis; c) identify IL-32 as a candidate mediator linking lipotoxicity to inflammation and liver disease. Although this precision medicine drug discovery pipeline is mainly being applied to non-alcoholic steatohepatitis, there is hope that successful products could be repurposed to treat alcohol-related liver disease as well. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34027340; info:eu-repo/semantics/altIdentifier/wos/WOS:000658290100023; volume:3; issue:3; firstpage:1; lastpage:13; numberofpages:13; journal:JHEP REPORTS; http://hdl.handle.net/2434/856718Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85105301258 |
| DOI: | 10.1016/j.jhepr.2021.100284 |
| الإتاحة: | https://doi.org/10.1016/j.jhepr.2021.100284Test http://hdl.handle.net/2434/856718Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6E5584B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jhepr.2021.100284 |
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