CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by depletion of motor neurons (MNs), for which effective medical treatments are still required. Previous transcriptomic analysis revealed the up-regulation of C-X-C motif chemokine receptor 2 (CXCR2)-mRNA in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Valentina La Cognata, Elisabetta Golini, Rosario Iemmolo, Sara Balletta, Giovanna Morello, Carla De Rosa, Ambra Villari, Sara Marinelli, Valentina Vacca, Gabriele Bonaventura, Paola Dell'Albani, Eleonora Aronica, Fabio Mammano, Silvia Mandillo, Sebastiano Cavallaro
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Amyotrophic lateral sclerosis CXCR2 IL-8 iPSC Motor neurons Neurodegeneration Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/eb3bd61adf9447c7a17fb9315972c47d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eb3bd61adf9447c7a17fb9315972c47d
record_format	dspace
spelling	oai:doaj.org-article:eb3bd61adf9447c7a17fb9315972c47d2021-11-12T04:26:36ZCXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice1095-953X10.1016/j.nbd.2021.105538https://doaj.org/article/eb3bd61adf9447c7a17fb9315972c47d2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121002874https://doaj.org/toc/1095-953XAmyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by depletion of motor neurons (MNs), for which effective medical treatments are still required. Previous transcriptomic analysis revealed the up-regulation of C-X-C motif chemokine receptor 2 (CXCR2)-mRNA in a subset of sporadic ALS patients and SOD1G93A mice. Here, we confirmed the increase of CXCR2 in human ALS cortex, and showed that CXCR2 is mainly localized in cell bodies and axons of cortical neurons. We also investigated the effects of reparixin, an allosteric inhibitor of CXCR2, in degenerating human iPSC-derived MNs and SOD1G93A mice. In vitro, reparixin rescued MNs from apoptotic cell death, preserving neuronal morphology, mitochondrial membrane potential and cytoplasmic membrane integrity, whereas in vivo it improved neuromuscular function of SOD1G93A mice. Altogether, these data suggest a role for CXCR2 in ALS pathology and support its pharmacological inhibition as a candidate therapeutic strategy against ALS at least in a specific subgroup of patients.Valentina La CognataElisabetta GoliniRosario IemmoloSara BallettaGiovanna MorelloCarla De RosaAmbra VillariSara MarinelliValentina VaccaGabriele BonaventuraPaola Dell'AlbaniEleonora AronicaFabio MammanoSilvia MandilloSebastiano CavallaroElsevierarticleAmyotrophic lateral sclerosisCXCR2IL-8iPSCMotor neuronsNeurodegenerationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 160, Iss , Pp 105538- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Amyotrophic lateral sclerosis CXCR2 IL-8 iPSC Motor neurons Neurodegeneration Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Amyotrophic lateral sclerosis CXCR2 IL-8 iPSC Motor neurons Neurodegeneration Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Valentina La Cognata Elisabetta Golini Rosario Iemmolo Sara Balletta Giovanna Morello Carla De Rosa Ambra Villari Sara Marinelli Valentina Vacca Gabriele Bonaventura Paola Dell'Albani Eleonora Aronica Fabio Mammano Silvia Mandillo Sebastiano Cavallaro CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
description	Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by depletion of motor neurons (MNs), for which effective medical treatments are still required. Previous transcriptomic analysis revealed the up-regulation of C-X-C motif chemokine receptor 2 (CXCR2)-mRNA in a subset of sporadic ALS patients and SOD1G93A mice. Here, we confirmed the increase of CXCR2 in human ALS cortex, and showed that CXCR2 is mainly localized in cell bodies and axons of cortical neurons. We also investigated the effects of reparixin, an allosteric inhibitor of CXCR2, in degenerating human iPSC-derived MNs and SOD1G93A mice. In vitro, reparixin rescued MNs from apoptotic cell death, preserving neuronal morphology, mitochondrial membrane potential and cytoplasmic membrane integrity, whereas in vivo it improved neuromuscular function of SOD1G93A mice. Altogether, these data suggest a role for CXCR2 in ALS pathology and support its pharmacological inhibition as a candidate therapeutic strategy against ALS at least in a specific subgroup of patients.
format	article
author	Valentina La Cognata Elisabetta Golini Rosario Iemmolo Sara Balletta Giovanna Morello Carla De Rosa Ambra Villari Sara Marinelli Valentina Vacca Gabriele Bonaventura Paola Dell'Albani Eleonora Aronica Fabio Mammano Silvia Mandillo Sebastiano Cavallaro
author_facet	Valentina La Cognata Elisabetta Golini Rosario Iemmolo Sara Balletta Giovanna Morello Carla De Rosa Ambra Villari Sara Marinelli Valentina Vacca Gabriele Bonaventura Paola Dell'Albani Eleonora Aronica Fabio Mammano Silvia Mandillo Sebastiano Cavallaro
author_sort	Valentina La Cognata
title	CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
title_short	CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
title_full	CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
title_fullStr	CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
title_full_unstemmed	CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice
title_sort	cxcr2 increases in als cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in sod1g93a mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/eb3bd61adf9447c7a17fb9315972c47d
work_keys_str_mv	AT valentinalacognata cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT elisabettagolini cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT rosarioiemmolo cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT saraballetta cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT giovannamorello cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT carladerosa cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT ambravillari cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT saramarinelli cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT valentinavacca cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT gabrielebonaventura cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT paoladellalbani cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT eleonoraaronica cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT fabiomammano cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT silviamandillo cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice AT sebastianocavallaro cxcr2increasesinalscorticalneuronsanditsinhibitionpreventsmotorneurondegenerationinvitroandimprovesneuromuscularfunctioninsod1g93amice
_version_	1718431323193868288

CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice

Ejemplares similares