Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11

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Autophagy is a degradative pathway for the removal and subsequent recycling of dysfunctional intracellular components. The material destined for degradation is initially enclosed by a double membrane, the autophagosome. In autolysosomes, which result from fusion of autophagosomes with lysosomes, the material is finally broken down. Recent in vitro data suggested that the protein Spatacsin plays a pivotal role in the regeneration of lysosomes from autolysosomes. Spatacsin is encoded by SPG11, the most common gene mutated in autosomal recessive hereditary spastic paraplegia. Here we show that mice devoid of Spatacsin develop symptoms consistent with spastic paraplegia and progressively loose cortical motoneurons and Purkinje cells. In these mice degenerating neurons have a reduced number of lysosomes available for fusion with autophagosomes and consequently accumulate autolysosome-derived material over time. In the long term this causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells.

Vyšlo v časopise: Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005454
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005454

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