Massive transcriptome sequencing of human spinal cord tissues provides new insights into motor neuron degeneration in ALS
Articolo
Data di Pubblicazione:
2017
Citazione:
Massive transcriptome sequencing of human spinal cord tissues provides new insights into motor neuron degeneration in ALS / A.M. D'Erchia, A. Gallo, C. Manzari, S. Raho, D.S. Horner, M. Chiara, A. Valletti, I. Aiello, F. Mastropasqua, L. Ciaccia, F. Locatelli, F. Pisani, G.P. Nicchia, M. Svelto, G. Pesole, E. Picardi. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017 Aug 30), pp. 10046.1-10046.20. [10.1038/s41598-017-10488-7]
Abstract:
ALS is a devastating and debilitating human disease characterized by the progressive death of upper and lower motor neurons. Although much effort has been made to elucidate molecular determinants underlying the onset and progression of the disorder, the causes of ALS remain largely unknown. In the present work, we have deeply sequenced whole transcriptome from spinal cord ventral horns of post-mortem ALS human donors affected by the sporadic form of the disease (which comprises â¼90% of the cases but which is less investigated than the inherited form of the disease). We observe 1160 deregulated genes including 18 miRNAs and show that down regulated genes are mainly of neuronal derivation while up regulated genes have glial origin and tend to be involved in neuroinflammation or cell death. Remarkably, we find strong deregulation of SNAP25 and STX1B at both mRNA and protein levels suggesting impaired synaptic function through SNAP25 reduction as a possible cause of calcium elevation and glutamate excitotoxicity. We also note aberrant alternative splicing but not disrupted RNA editing.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Amyotrophic-lateral-sclerosis; sporadic ALS; mouse model; brain; expression; proteins; disease; mice; differentiation; identification
Elenco autori:
A.M. D'Erchia, A. Gallo, C. Manzari, S. Raho, D.S. Horner, M. Chiara, A. Valletti, I. Aiello, F. Mastropasqua, L. Ciaccia, F. Locatelli, F. Pisani, G.P. Nicchia, M. Svelto, G. Pesole, E. Picardi
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