Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons

SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their...
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Autor*in:	Jonathan Gilley [verfasserIn] Giuseppe Orsomando [verfasserIn] Isabel Nascimento-Ferreira [verfasserIn] Michael P. Coleman [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Übergeordnetes Werk:	In: Cell Reports - Elsevier, 2015, 10(2015), 12, Seite 1974-1981
Übergeordnetes Werk:	volume:10 ; year:2015 ; number:12 ; pages:1974-1981

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.celrep.2015.02.060

Katalog-ID:	DOAJ032603916

Internformat


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author_variant	j g jg g o go i n f inf m c mc
matchkey_str	article:22111247:2015----::becosr1ecedvlpetnsriaonn
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publishDate	2015
allfields	10.1016/j.celrep.2015.02.060 doi (DE-627)DOAJ032603916 (DE-599)DOAJ8ad2162bda0d4a0682c72aef15edbd5d DE-627 ger DE-627 rakwb eng QH301-705.5 Jonathan Gilley verfasserin aut Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies. Biology (General) Giuseppe Orsomando verfasserin aut Isabel Nascimento-Ferreira verfasserin aut Michael P. Coleman verfasserin aut In Cell Reports Elsevier, 2015 10(2015), 12, Seite 1974-1981 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:10 year:2015 number:12 pages:1974-1981 https://doi.org/10.1016/j.celrep.2015.02.060 kostenfrei https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124715002375 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 10 2015 12 1974-1981
spelling	10.1016/j.celrep.2015.02.060 doi (DE-627)DOAJ032603916 (DE-599)DOAJ8ad2162bda0d4a0682c72aef15edbd5d DE-627 ger DE-627 rakwb eng QH301-705.5 Jonathan Gilley verfasserin aut Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies. Biology (General) Giuseppe Orsomando verfasserin aut Isabel Nascimento-Ferreira verfasserin aut Michael P. Coleman verfasserin aut In Cell Reports Elsevier, 2015 10(2015), 12, Seite 1974-1981 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:10 year:2015 number:12 pages:1974-1981 https://doi.org/10.1016/j.celrep.2015.02.060 kostenfrei https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124715002375 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 10 2015 12 1974-1981
allfields_unstemmed	10.1016/j.celrep.2015.02.060 doi (DE-627)DOAJ032603916 (DE-599)DOAJ8ad2162bda0d4a0682c72aef15edbd5d DE-627 ger DE-627 rakwb eng QH301-705.5 Jonathan Gilley verfasserin aut Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies. Biology (General) Giuseppe Orsomando verfasserin aut Isabel Nascimento-Ferreira verfasserin aut Michael P. Coleman verfasserin aut In Cell Reports Elsevier, 2015 10(2015), 12, Seite 1974-1981 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:10 year:2015 number:12 pages:1974-1981 https://doi.org/10.1016/j.celrep.2015.02.060 kostenfrei https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124715002375 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 10 2015 12 1974-1981
allfieldsGer	10.1016/j.celrep.2015.02.060 doi (DE-627)DOAJ032603916 (DE-599)DOAJ8ad2162bda0d4a0682c72aef15edbd5d DE-627 ger DE-627 rakwb eng QH301-705.5 Jonathan Gilley verfasserin aut Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies. Biology (General) Giuseppe Orsomando verfasserin aut Isabel Nascimento-Ferreira verfasserin aut Michael P. Coleman verfasserin aut In Cell Reports Elsevier, 2015 10(2015), 12, Seite 1974-1981 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:10 year:2015 number:12 pages:1974-1981 https://doi.org/10.1016/j.celrep.2015.02.060 kostenfrei https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124715002375 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 10 2015 12 1974-1981
allfieldsSound	10.1016/j.celrep.2015.02.060 doi (DE-627)DOAJ032603916 (DE-599)DOAJ8ad2162bda0d4a0682c72aef15edbd5d DE-627 ger DE-627 rakwb eng QH301-705.5 Jonathan Gilley verfasserin aut Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies. Biology (General) Giuseppe Orsomando verfasserin aut Isabel Nascimento-Ferreira verfasserin aut Michael P. Coleman verfasserin aut In Cell Reports Elsevier, 2015 10(2015), 12, Seite 1974-1981 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:10 year:2015 number:12 pages:1974-1981 https://doi.org/10.1016/j.celrep.2015.02.060 kostenfrei https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124715002375 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 10 2015 12 1974-1981
language	English
source	In Cell Reports 10(2015), 12, Seite 1974-1981 volume:10 year:2015 number:12 pages:1974-1981
sourceStr	In Cell Reports 10(2015), 12, Seite 1974-1981 volume:10 year:2015 number:12 pages:1974-1981
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Biology (General)
isfreeaccess_bool	true
container_title	Cell Reports
authorswithroles_txt_mv	Jonathan Gilley @@aut@@ Giuseppe Orsomando @@aut@@ Isabel Nascimento-Ferreira @@aut@@ Michael P. Coleman @@aut@@
publishDateDaySort_date	2015-01-01T00:00:00Z
hierarchy_top_id	684964562
id	DOAJ032603916
language_de	englisch
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callnumber-first	Q - Science
author	Jonathan Gilley
spellingShingle	Jonathan Gilley misc QH301-705.5 misc Biology (General) Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
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topic_title	QH301-705.5 Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
topic	misc QH301-705.5 misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc Biology (General)
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title	Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
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title_full	Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
author_sort	Jonathan Gilley
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author_browse	Jonathan Gilley Giuseppe Orsomando Isabel Nascimento-Ferreira Michael P. Coleman
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title_sort	absence of sarm1 rescues development and survival of nmnat2-deficient axons
callnumber	QH301-705.5
title_auth	Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
abstract	SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies.
abstractGer	SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies.
abstract_unstemmed	SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, independently of NMNAT metabolites, preventing perinatal lethality. Furthermore, NAMPT inhibition partially restores outgrowth of NMNAT2-deficient axons, suggesting that the NMNAT substrate, NMN, contributes to this phenotype. NMNAT2-depletion-dependent degeneration of established axons and restricted extension of developing axons are thus both SARM1 dependent, and SARM1 acts either downstream of NMNAT2 loss and NMN accumulation in a linear pathway or in a parallel branch of a convergent pathway. Understanding the pathway will help establish relationships with other modulators of axon survival and facilitate the development of effective therapies for axonopathies.
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title_short	Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons
url	https://doi.org/10.1016/j.celrep.2015.02.060 https://doaj.org/article/8ad2162bda0d4a0682c72aef15edbd5d http://www.sciencedirect.com/science/article/pii/S2211124715002375 https://doaj.org/toc/2211-1247
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up_date	2024-07-04T01:49:47.576Z
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Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons

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