University of Zagreb. Faculty of Science. Department of Biology.
Abstract
Lizosomi su primarni katabolički odjeljci eukariotskih stanica. Za funkciju lizosoma neophodne su dvije skupine proteina: kisele hidrolaze i integralni lizosomalni membranski proteini. Lizosomi su uključeni u različite fiziološke procese kao što su homeostaza kolesterola, popravak plazma membrane, obrana od patogena, stanična smrt i stanična signalizacija. Uzrok lizosomalnih bolesti nakupljanja lipida je u većini slučajeva neispravna aktivnost lizosomalnih proteina što rezultira akumuliranjem nerazgrađenih metabolita unutar lizosoma. Postoji sve više dokaza da su lizosomi uključeni i u proces patogeneze različitih neurodegenerativnih bolesti uključujući Alzheimerovu bolest, Parkinsonovu bolest te Huntingtonovu bolest. Promijenjen metabolizam lipida uzrokuje disfunkciju endosomalnog/lizosomalnog puta. Pretpostavlja se da je nefunkcionalna razgradnja proteina inducirana disfunkcijom endosomalno/lizosomalnog sustava primarni uzrok nakupljanja proteina te nastanka neurodegenerativnih bolesti. U ovom sam seminarskom radu dala kratak osvrt na strukturu i funkciju lizosoma, promjenu metabolizma lipida u lizosomalnim bolestima nakupljanja lipida te na disfunkciju endosomalno/lizosomalnog sustava u neurodegenerativnim bolestima.Lysosomes are the primary catabolic compartments of eukaryotic cells. Two classes of proteins are essential for the lysosome function: lysosomal hydrolases and integral lysosomal membrane proteins. Lysosomes are involved in various physiological processes, such as cholesterol homeostasis, plasma membrane repair, pathogen defence, cell death and cell signalling. Lysosomal storage disorders (LSD) are mainly caused by the defective activity of lysosomal proteins, which results in the intra-lysosomal accumulation of undegraded metabolites. There is increasing evidence that lysosomes are also involved in the pathogenesis of a variety of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Endosomal/lysosomal dysfunction is caused by altered lipid metabolism. It is hypothesized that abnormal protein degradation and deposition caused by endosomal/lysosomal dysfunction may be the primary trigger of age-related neurodegeneration. In this review, the structure and function of lysosomes, the role of abnormal lipid metabolism in relation to aberrant endosomal/lysosomal function and the relationship between lysosome dysfunction and various neurodegenerative diseases is described
