RBI Scientists Publish New Article in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
RBI scientist Dr. Silva Katušić Hećimović and colleagues Martina Malnar and Marko Košićek in the Laboratory for molecular neuropharmacology, Department of Molecular Medicine have published a paper entitled Niemann Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the beta-secretase pathway in the journal Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. This work is the result of a collaboration between Dr. Katušić Hećimović and scientists from the USA (NIH-FIRCA project) and Germany (DAAD-MZOŠ bilateral project).
The paper documents results wich contribute to our understanding of the mechanism of action of cholesterol in the pathogenesis of Alzheimer's disease. Malnar et al. Show that an elevated level of cholesterol leads to decreased expression of the APP protein on the surface of the cell as well as increased proteolysis of this protein by the enzyme beta-secretase. This leads to an increase in the production of the beta amyloid peptide a major causative agent in Alzheimer's disease. These results, in contrast to previous studies in the literature, shows that cholesterol can affect APP protein localization and suggests that defects in endocytosis could be the trigger that leads to increased production of beta amyloid peptide and the onset of Alzheimer's disease.