Finding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: opportunities for shared therapeutic interventions

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dc.catalogadoryvc
dc.contributor.authorYañez Henríquez, María José
dc.contributor.authorMarín Marín, Tamara Alejandra
dc.contributor.authorBalboa Castillo, Elisa
dc.contributor.authorKlein Posternack, Andrés David
dc.contributor.authorÁlvarez, Alejandra R.
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.date.accessioned2024-06-06T19:19:44Z
dc.date.available2024-06-06T19:19:44Z
dc.date.issued2020
dc.description.abstractLysosomal storage disorders (LSDs) are diseases characterized by the accumulation of macromolecules in the late endocytic system and are caused by inherited defects in genes that encode mainly lysosomal enzymes or transmembrane lysosomal proteins. Niemann-Pick type C disease (NPCD), a LSD characterized by liver damage and progressive neurodegeneration that leads to early death, is caused by mutations in the genes encoding the NPC1 or NPC2 proteins. Both proteins are involved in the transport of cholesterol from the late endosomal compartment to the rest of the cell. Loss of function of these proteins causes primary cholesterol accumulation, and secondary accumulation of other lipids, such as sphingolipids, in lysosomes. Despite years of studying the genetic and molecular bases of NPCD and related-lysosomal disorders, the pathogenic mechanisms involved in these diseases are not fully understood. In this review we will summarize the pathogenic mechanisms described for NPCD and we will discuss their relevance for other LSDs with neurological components such as Niemann- Pick type A and Gaucher diseases. We will particularly focus on the activation of signaling pathways that may be common to these three pathologies with emphasis on how the intra-lysosomal accumulation of lipids leads to pathology, specifically to neurological impairments. We will show that although the primary lipid storage defect is different in these three LSDs, there is a similar secondary accumulation of metabolites and activation of signaling pathways that can lead to common pathogenic mechanisms. This analysis might help to delineate common pathological mechanisms and therapeutic targets for lysosomal storage diseases.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.bbadis.2020.165875
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2020.165875
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86570
dc.information.autorucFacultad de Ciencias Biológicas;Yañez Henríquez, María José;S/I;197587
dc.information.autorucEscuela de Medicina;Marín Marín, Tamara Alejandra;S/I;249923
dc.information.autorucFacultad de Ciencias Biológicas;Balboa Castillo, Elisa;142402
dc.information.autorucFacultad de Ciencias Biológicas;Klein Posternack, Andrés David;S/I;2966
dc.information.autorucEscuela de Medicina; Zanlungo Matsuhiro, Silvana; 0000-0001-8383-9829; 72650
dc.language.isoen
dc.nota.accesocontenido parcial
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleFinding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: opportunities for shared therapeutic interventions
dc.typeartículo
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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