SNCA protein product, alpha-synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson’s Disease, but research efforts are still needed to elucidate its physiological functions and regulation. In this work, we aim to characterize the long non-coding RNA SNCA-AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. SH-SY5Y cells were stably transfected with either SNCA-AS1 or SNCA and through RNAsequencing we assessed their transcriptional signature. Real Time-PCR and western blot were also used to verify SNCA-AS1’s effect on SNCA’s expression, and neurite extension was assessed via immunofluorescence analysis. The overexpression of SNCA-AS1 upregulates SNCA mRNA and protein, and both genes appear to strongly impact neurite extension and synapses’ biology, through specific molecular signatures. We found a reduced expression of markers associated with synaptic plasticity, and we specifically focus on GABAergic and dopaminergic synapses, for their relevance in aging processes and PD, respectively. As part of this signature is co-regulated by the two genes, we discriminate between functions elicited by genes specifically altered by SNCA-AS1 or SNCA’s overexpression, and we observed a highly relevant role for solely SNCA-AS1. We also highlight how numerous deregulated pathways are implicated in aging-related processes, suggesting that SNCA-AS1 could be a key player in cellular senescence, with implications for aging-related diseases. Specifically, the upregulation of SNCA-AS1 leads to alterations in numerous PD specific genes, with an impact highly comparable to that of SNCA. SNCA/SNCA-AS1 ratio is also significantly altered in PBMCs from PD patients versus healthy controls. Our results show that SNCA-AS1 elicits its cellular functions not only through the regulation of SNCA, but also through a selective and specific modulation of synaptogenesis and senescence, with strong implications for PD.

Implications for alpha-synuclein antisense transcript SNCA-AS1 in Parkinson’s Disease: role in synaptogenesis and aging-related pathways / F. Rey, C. Pandini, L. Messa, R. Launi, R. Zangaglia, G.V. Zuccotti, S. Gagliardi, C. Cereda, S. Carelli. ((Intervento presentato al 19. convegno 19th SINS National Congress tenutosi a Virtual Congress : 9-11 September nel 2021.

Implications for alpha-synuclein antisense transcript SNCA-AS1 in Parkinson’s Disease: role in synaptogenesis and aging-related pathways

F. Rey;C. Pandini;G.V. Zuccotti;S. Carelli
Co-ultimo
2021

Abstract

SNCA protein product, alpha-synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson’s Disease, but research efforts are still needed to elucidate its physiological functions and regulation. In this work, we aim to characterize the long non-coding RNA SNCA-AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. SH-SY5Y cells were stably transfected with either SNCA-AS1 or SNCA and through RNAsequencing we assessed their transcriptional signature. Real Time-PCR and western blot were also used to verify SNCA-AS1’s effect on SNCA’s expression, and neurite extension was assessed via immunofluorescence analysis. The overexpression of SNCA-AS1 upregulates SNCA mRNA and protein, and both genes appear to strongly impact neurite extension and synapses’ biology, through specific molecular signatures. We found a reduced expression of markers associated with synaptic plasticity, and we specifically focus on GABAergic and dopaminergic synapses, for their relevance in aging processes and PD, respectively. As part of this signature is co-regulated by the two genes, we discriminate between functions elicited by genes specifically altered by SNCA-AS1 or SNCA’s overexpression, and we observed a highly relevant role for solely SNCA-AS1. We also highlight how numerous deregulated pathways are implicated in aging-related processes, suggesting that SNCA-AS1 could be a key player in cellular senescence, with implications for aging-related diseases. Specifically, the upregulation of SNCA-AS1 leads to alterations in numerous PD specific genes, with an impact highly comparable to that of SNCA. SNCA/SNCA-AS1 ratio is also significantly altered in PBMCs from PD patients versus healthy controls. Our results show that SNCA-AS1 elicits its cellular functions not only through the regulation of SNCA, but also through a selective and specific modulation of synaptogenesis and senescence, with strong implications for PD.
10-set-2021
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Società Italiana di Neuroscienze
Implications for alpha-synuclein antisense transcript SNCA-AS1 in Parkinson’s Disease: role in synaptogenesis and aging-related pathways / F. Rey, C. Pandini, L. Messa, R. Launi, R. Zangaglia, G.V. Zuccotti, S. Gagliardi, C. Cereda, S. Carelli. ((Intervento presentato al 19. convegno 19th SINS National Congress tenutosi a Virtual Congress : 9-11 September nel 2021.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/937770
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