title: Expression of the Parkinson's Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32.
abstract: Alpha-synuclein is an abundant neuronal protein which has been associated with physiological processes like synaptic function, neurogenesis, and neuronal differentiation but also with pathological neurodegeneration. Indeed, alpha-synuclein (snca) is one of the major genes implicated in Parkinson's disease (PD). However, little is known about the regulation of alpha-synuclein expression. Unveiling the mechanisms that control its regulation is of high importance, as it will enable to further investigate and comprehend the physiological role of alpha-synuclein as well as its potential contribution in the aetiology of PD. Previously, we have shown that the protein TRIM32 regulates fate specification of neural stem cells. Here, we investigated the impact of TRIM32 on snca expression regulation in vitro and in vivo in neural stem cells and neurons. We demonstrated that TRIM32 is positively influencing snca expression in a neuronal cell line, while the absence of TRIM32 is causing deregulated levels of snca transcripts. Finally, we provided evidence that TRIM32 binds to the promoter region of snca, suggesting a novel mechanism of its transcriptional regulation. On the one hand, the presented data link the PD-associated gene alpha-synuclein to the neuronal cell fate determinant TRIM32 and thereby support the concept that PD is a neurodevelopmental disorder. On the other hand, they imply that defects in olfactory bulb adult neurogenesis might contribute to early PD-associated non-motor symptoms like hyposmia.
authors.affiliation: Developmental and Cellular Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg.
authors.forename: Maria Angeliki S
authors.initials: MAS
authors.lastname: Pavlou
authors.affiliation: Systems control group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg.
authors.forename: Nicoló
authors.initials: N
authors.lastname: Colombo
authors.affiliation: Instituto de Biomedicina (IBIOMED), Department of Molecular Biology, Universidad de León, Campus de Vegazana, León, 24071, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fuertes-Alvarez
authors.affiliation: Developmental and Cellular Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicklas
authors.affiliation: Developmental and Cellular Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg.
authors.forename: Laura Gonzalez
authors.initials: LG
authors.lastname: Cano
authors.affiliation: Instituto de Biomedicina (IBIOMED), Department of Molecular Biology, Universidad de León, Campus de Vegazana, León, 24071, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Marín
authors.affiliation: Systems control group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg.
authors.forename: Jorge
authors.initials: J
authors.lastname: Goncalves
authors.affiliation: Developmental and Cellular Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 avenue du Swing, 4367, Belvaux, Luxembourg. jens.schwamborn@uni.lu.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D009830:Olfactory Bulb / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000072160:Tumor Protein p73; D051844:alpha-Synuclein; C514011:TRIM32 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Alpha-synuclein; Neuronal differentiation; TRIM32; Transcriptional regulation