Guest lectures at MedILS

Tuesday, 24 May 2022, 14:00-16:00 h

Niemann-Pick type C disease (NPC) is a rare inherited lipid storage disorder caused by mutations in NPC1 or NPC2 gene (95% or 5% of the cases, respectively). It is characterized by accumulation of cholesterol in late endosomes / lysosomes leading to progressive neurodegeneration (of primarily Purkinje neurons in cerebellum) and neuroinflammation. NPC disease is manifested by a variety of neurological (and non-neurological) symptoms. As no effective disease-modifying treatment is available for NPC, most patients die between 10 and 25 years of age. NPC imposes an emotional and economic burden on patients, families and society. It is therefore of high priority to develop new therapies to attenuate this devastating disease. It is intriguing that a rare NPC disease shows several key features of a common and complex Alzheimer's disease (AD) including accumulation of amyloid-β (Aβ) peptides and hyperphosphorylation of tau. We have previously shown that AD-like phenotype in NPC disease may partly be due to trafficking defect within the endolysosomal pathway leading to enhanced proteolysis by BACE1 (β-secretase) - a central enzyme in the pathogenesis of AD. Alterations were identified already within early endosomal compartments indicating defective endosome biogenesis in NPC. Defects of the endolysosomal pathway are shared by other lysosomal storage disorders as well as the more common Alzheimer's and Parkinson's disease (AD and PD). Hence, the knowledge gained through studies on NPC disease could be used to better understand more common neurodegenerative disorders, such as AD and PD.