ArticlePloS one2012
Transcriptional and post-transcriptional regulation of SPAST, the gene most frequently mutated in hereditary spastic paraplegia.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- FBXL17/spastin axis as a novel therapeutic target of hereditary spastic paraplegia.Cell & bioscience · 2022Article
- The Role of Spastin in Axon Biology.Frontiers in cell and developmental biology · 2022Review
- Molecular and cellular mechanisms of spastin in neural development and disease (Review).International journal of molecular medicine · 2021Review
- Clinical Characterization of 2 Siblings with a Homozygous SPAST Variant.The American journal of case reports · 2020Article
- The lncRNA MALAT1/miR-30/Spastin Axis Regulates Hippocampal Neurite Outgrowth.Frontiers in cellular neuroscience · 2020Article
- Article
- Mutations in the SPAST gene causing hereditary spastic paraplegia are related to global topological alterations in brain functional networks.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Article
- Elk1 affects katanin and spastin proteins via differential transcriptional and post-transcriptional regulations.PloS one · 2019Article
- Clinical Trial Designs and Measures in Hereditary Spastic Paraplegias.Frontiers in neurology · 2018Review
- New perspectives on the development of muscle contractures following central motor lesions.The Journal of physiology · 2017Review
- Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis.Oncotarget · 2016Review
- Article
- Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia.Molecular neurodegeneration · 2015Review
- The genetics of hair cell development and regeneration.Annual review of neuroscience · 2013Review
- Article
- Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis.American journal of human genetics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70-80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3'-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP.
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Registered trials
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