Optineurin u neurodegenerativnim bolestima

Od otkrića optineurina do danas pronađene su brojne mutacije u optineurinu koje se povezuju s nastankom nekoliko različitih bolesti: glaukomom, amiotrofičnom lateralnom sklerozom (ALS) i frontotemporalnom demencijom (FTD). Nadalje, poliformizmi koji dovode do smanjene ekspresije optineurina povezani su s Pagetovom bolesti kostiju i upalnom bolešću crijeva. Optineurin sudjeluje u brojnim staničnim procesima u kojima mu se pridaje protektivna uloga. Ovim radom bit će sažeta uloga optineurina u neuroinflamaciji, autofagiji, procesima staničnog transporta i nekroptozi, s istaknutim fokusom na utjecaj mutacija u optineurinu na neurodegeneraciju, odnosno povezanost s mehanizmima nastanka ALS-a i glaukoma. Mutacije u optineurinu dostatne su da naruše homeostazu staničnih procesa u kojima sudjeluje. Zanimljivo je da ALS i FTD uzrokuju iste, a glaukom različite mutacije u optineurinu, sugerirajući preklapanje patogeneze ALS-a i FTD-a te različitu patogenezu glaukoma.Since the discovery of optineurin, numerous mutations in optineurin have been found to be associated with the onset of several different diseases: glaucoma, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Furthermore, polymorphisms leading to decreased optineurin expression have been associated with Paget’s disease of bone and inflammatory bowel disease. Optineurin participates in a number of cellular processes in which it was assigned a protective role. This paper summarizes the role of optineurin in neuroinflammation, autophagy, cell trafficking and necroptosis. A prominent focus is the impact of mutations in optineurin on neurodegeneration, or their relationship with pathogenesis of ALS and glaucoma. Mutations in optineurin are sufficient to disrupt the homeostasis of cellular processes in which it participates. Interestingly, ALS and FTD are caused by the same mutations, whereas glaucoma is caused by different mutations in optineurin, suggesting an overlapping pathogenesis of ALS and FTD, and distinct pathogenesis of glaucoma