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

AbstractAlpha-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 ofalpha-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 onsnca expression regulation in vitro and in vivo in neural stem cells and neurons. We demonstrated that TRIM32 is positively influencingsnca expression in a neuronal cell line, while the absence of TRIM32 is causing deregulated levels ofsnca transcripts. Finally, we provided evidence that TRIM32 binds to the promoter region ofsnca, suggesting a novel mechanism of its transcriptional regulation. On the one hand, the presented data link the PD-associated genealpha-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-...
Source: Molecular Neurobiology - Category: Neurology Source Type: research