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Expression of the Parkinson’s Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32

Pavlou, MAS; Colombo, N; Fuertes-Alvarez, S; Nicklas, S; Cano, LG; Marín, MC; Goncalves, J; (2016) Expression of the Parkinson’s Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32. Molecular Neurobiology , 54 (6) pp. 4257-4270. 10.1007/s12035-016-9989-9. Green open access

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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.

Type: Article
Title: Expression of the Parkinson’s Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12035-016-9989-9
Publisher version: https://doi.org/10.1007/s12035-016-9989-9
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alpha-synuclein, TRIM32, Transcriptional regulation, Neuronal differentiation
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10059507
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