Project description:The goal of this project is to study differentially expressed genes in patients affected by Hereditary Spastic Paraplegia (HSP) linked to mutations of the gene encoding spastin an ubiquitously expressed protein that has recently been shown to be involved in microtubule regulation and vesicle trafficking by cell culture studies. Gene profiling was done with Affymetrix U95Av2 GeneChips using the total RNA extracted from muscle biopsies of 3 SPG4-linked HSP patients. Keywords: other
Project description:The goal of this project is to study differentially expressed genes in patients affected by Hereditary Spastic Paraplegia (HSP) linked to mutations of the gene encoding spastin an ubiquitously expressed protein that has recently been shown to be involved in microtubule regulation and vesicle trafficking by cell culture studies. Gene profiling was done with Affymetrix U95Av2 GeneChips using the total RNA extracted from muscle biopsies of 3 SPG4-linked HSP patients.
Project description:To understand the disease mechanism of SPG7 hereditary spastic paraplegia, we generated and evaluated patient and control induced pluripotent stem cell derived cortical neurons. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2023-05-30 | GSE233258 | GEO
Project description:SPAST variant that causes hereditary spastic paraplegia
Project description:We investigated brain tissue from N471D WASH complex subunit strumpellin knock-in mice as a genetic model for hereditary spastic paraplegia type 8. While WASHC5-related protein interaction partners and complexes showed no change in abundancies, the proteomic analysis depicted consistent upregulation of BPTF and downregulation of KLHL11 in heterozygous and homozygous knock-in mice. This finding suggests mechanistic links for hereditary spastic paraplegia type 8 through the roles of BPTF and KLHL11 in neurodegeneration and protein quality control, respectively.
Project description:The human spastizin (spastic paraplegia 15, SPG15) and spatacsin (spastic paraplegia 11, SPG11) complex is involved in the formation of lysosomes, and mutations in these two proteins are linked with hereditary autosomal recessive spastic paraplegia (HSP). SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes. We employed cryo-electron microscopy and in silico predictions to investigate the structural assemblies of SPG11-SPG15 and AP5:SPG11-SPG15 complex. The W-shaped SPG11-SPG15 intertwined in a head-to-head fashion, and the N-terminal region of SPG11 is required for AP5 complex interaction and assembly. The AP5 complex is in a super open conformation. Our findings reveal that the AP5:SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodelling in vitro. These studies provide key insights into the structure and function of the spastic paraplegia AP5:SPG11-SPG15 complex, which is essential for the initiation of autolysosome tubulation.
2025-03-20 | PXD054972 | Pride
Project description:Toxoplasmosis accelerates the progression of hereditary spastic paraplegia
| PRJNA1110596 | ENA
Project description:Genetic variants of patients with hereditary spastic paraplegia