Gene identification in Hereditary Spastic Paraplegias and characterization of Spastic Paraplegia type 58 (SPG58)

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dc.contributor.advisor Schöls, Ludger (Prof.Dr.) Caballero García de Oteyza, Andrés 2016-11-15T08:29:26Z 2016-11-15T08:29:26Z 2016-11
dc.identifier.other 479745749 de_DE
dc.identifier.uri de_DE
dc.description.abstract Hereditary spastic paraplegias (HSPs) are a large group of inherited neurodegenerative disorders characterised by a progressive spasticity and weakness of the lower limbs. Additional symptoms variably occur and define so-called complicated forms of the disease. HSPs exhibit a very high genetic and clinical variability, with at least 84 loci identified and 67 known causative genes. They can be inherited in autosomal dominant, autosomal recessive, and X-linked manner. However, they all share a common trait: a progressive lengthdependent distal axonopathy of the motor neurons that form the corticospinal tracts. The use of whole exome sequencing (WES) has dramatically increased the speed of gene discovery in HSP. This technique granted the conjunct identification of the five genes described here, which are responsible for causing different forms of spastic paraplegia: SPG28, SPG46, SPG26, SPG54 and SPG58. These genes are respectively involved in mitochondrial function, different aspects of lipid metabolism and RNA metabolism. The in-depth study of SPG58 shows how mutations in KIF1C alter the cellular localization of KIF1C protein and affect endogenous protein levels if mutations locate to the ATP-binding domain. This work also elucidates that KIF1C interacts with known RNA-binding proteins (RBPs) and that it also binds RNA directly and is thus itself an RBP. Transcripts bound to KIF1C correspond to genes involved in key mechanisms of cell cycle and gene regulation and in various aspects of RNA metabolism. In addition to the enrichment of ribosomal RNAs, KIF1C also interacts with ribosomal proteins and influences cellular ribosome distribution. This suggests that KIF1C might have a role in the regulation and or transport of ribosomes. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification Degeneration , Wissenschaft , Querschnittslähmung , Gehirn , Nervenzelle , Kinesin , RNS de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 610 de_DE
dc.subject.other HSPs en
dc.subject.other RNA en
dc.subject.other Ribosomal transport en
dc.subject.other KIF1C en
dc.subject.other spastic paraplegia en
dc.subject.other SPG58 en
dc.subject.other Neurodegeneration de_DE
dc.subject.other Gene identification en
dc.subject.other RNA-binding protein en
dc.title Gene identification in Hereditary Spastic Paraplegias and characterization of Spastic Paraplegia type 58 (SPG58) en
dc.type Dissertation de_DE
dcterms.dateAccepted 2016-10-14
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE


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