AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury
Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterize...
Gespeichert in:
| Veröffentlicht in: | Nature metabolism 2020-09, Vol.2 (9), p.918-933 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 933 |
|---|---|
| container_issue | 9 |
| container_start_page | 918 |
| container_title | Nature metabolism |
| container_volume | 2 |
| creator | Kong, Guiping Zhou, Luming Serger, Elisabeth Palmisano, Ilaria De Virgiliis, Francesco Hutson, Thomas H. Mclachlan, Eilidh Freiwald, Anja La Montanara, Paolo Shkura, Kirill Puttagunta, Radhika Di Giovanni, Simone |
| description | Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Whereas peripheral axons regenerate well after injury, axons located in the central nervous system, such as in the spinal cord, do not. Kong et al. identify AMPK as a regulator of neuronal regeneration and show that deletion of AMPKα1 promotes regeneration of injured spinal cord axons in mice. |
| doi_str_mv | 10.1038/s42255-020-0252-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2432854215</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2432854215</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-65e89ba2d463a347f76243391d12a6f0f619a2d970801d7f4e02397ebda634863</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EolXpB7BBXrIJ-JXXsqp4iSJYwNpykklIldrFkyD69zhqQaxYWGPNvXMWh5Bzzq44k9k1KiHiOGKChReLSB6RaZgiijMujv_8J2SOuGaMCc4VF_kpmUiRplkm1ZRsFk8vj7R0tveuQ9q_AzVfzpqOemjAgjd9-xl2Rdu1_Y66mlbO4xg719PG2KZrDUWw6PyOWhi8s0hN3YOnuG1HUOl8RVu7HvzujJzUpkOYH-aMvN3evC7vo9Xz3cNysYpKFcs-SmLI8sKISiXSSJXWaSKUlDmvuDBJzeqE5yHNU5YxXqW1AiZknkJRmUSqLJEzcrnnbr37GAB7vWmxhK4zFtyAOtBEFivB41Dl-2rpHaKHWm99uzF-pznTo2i9F62DaD2K1jLcXBzwQ7GB6vfiR2soiH0BQ2Qb8HrtBh9k4D_UbxfCiLw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2432854215</pqid></control><display><type>article</type><title>AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Kong, Guiping ; Zhou, Luming ; Serger, Elisabeth ; Palmisano, Ilaria ; De Virgiliis, Francesco ; Hutson, Thomas H. ; Mclachlan, Eilidh ; Freiwald, Anja ; La Montanara, Paolo ; Shkura, Kirill ; Puttagunta, Radhika ; Di Giovanni, Simone</creator><creatorcontrib>Kong, Guiping ; Zhou, Luming ; Serger, Elisabeth ; Palmisano, Ilaria ; De Virgiliis, Francesco ; Hutson, Thomas H. ; Mclachlan, Eilidh ; Freiwald, Anja ; La Montanara, Paolo ; Shkura, Kirill ; Puttagunta, Radhika ; Di Giovanni, Simone</creatorcontrib><description>Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Whereas peripheral axons regenerate well after injury, axons located in the central nervous system, such as in the spinal cord, do not. Kong et al. identify AMPK as a regulator of neuronal regeneration and show that deletion of AMPKα1 promotes regeneration of injured spinal cord axons in mice.</description><identifier>ISSN: 2522-5812</identifier><identifier>EISSN: 2522-5812</identifier><identifier>DOI: 10.1038/s42255-020-0252-3</identifier><identifier>PMID: 32778834</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/89 ; 14/19 ; 42 ; 42/44 ; 45 ; 45/91 ; 631/378 ; 631/443/319 ; 631/80 ; 64 ; 64/60 ; 82 ; 82/58 ; AMP-Activated Protein Kinases - metabolism ; Animals ; ATPases Associated with Diverse Cellular Activities - metabolism ; Axonal Transport ; Axons ; Axotomy ; Biomedical and Life Sciences ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; Female ; Ganglia, Spinal - metabolism ; Ganglia, Spinal - pathology ; Life Sciences ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration ; Proteasome Endopeptidase Complex - metabolism ; Proteomics ; Sciatic Nerve - metabolism ; Sciatic Nerve - pathology ; Sensory Receptor Cells - metabolism ; Sensory Receptor Cells - pathology ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - pathology</subject><ispartof>Nature metabolism, 2020-09, Vol.2 (9), p.918-933</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-65e89ba2d463a347f76243391d12a6f0f619a2d970801d7f4e02397ebda634863</citedby><cites>FETCH-LOGICAL-c453t-65e89ba2d463a347f76243391d12a6f0f619a2d970801d7f4e02397ebda634863</cites><orcidid>0000-0003-3154-5399 ; 0000-0002-7139-8090 ; 0000-0002-1722-0910 ; 0000-0001-7674-8064 ; 0000-0001-6795-2688</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s42255-020-0252-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s42255-020-0252-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32778834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kong, Guiping</creatorcontrib><creatorcontrib>Zhou, Luming</creatorcontrib><creatorcontrib>Serger, Elisabeth</creatorcontrib><creatorcontrib>Palmisano, Ilaria</creatorcontrib><creatorcontrib>De Virgiliis, Francesco</creatorcontrib><creatorcontrib>Hutson, Thomas H.</creatorcontrib><creatorcontrib>Mclachlan, Eilidh</creatorcontrib><creatorcontrib>Freiwald, Anja</creatorcontrib><creatorcontrib>La Montanara, Paolo</creatorcontrib><creatorcontrib>Shkura, Kirill</creatorcontrib><creatorcontrib>Puttagunta, Radhika</creatorcontrib><creatorcontrib>Di Giovanni, Simone</creatorcontrib><title>AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury</title><title>Nature metabolism</title><addtitle>Nat Metab</addtitle><addtitle>Nat Metab</addtitle><description>Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Whereas peripheral axons regenerate well after injury, axons located in the central nervous system, such as in the spinal cord, do not. Kong et al. identify AMPK as a regulator of neuronal regeneration and show that deletion of AMPKα1 promotes regeneration of injured spinal cord axons in mice.</description><subject>13/89</subject><subject>14/19</subject><subject>42</subject><subject>42/44</subject><subject>45</subject><subject>45/91</subject><subject>631/378</subject><subject>631/443/319</subject><subject>631/80</subject><subject>64</subject><subject>64/60</subject><subject>82</subject><subject>82/58</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>ATPases Associated with Diverse Cellular Activities - metabolism</subject><subject>Axonal Transport</subject><subject>Axons</subject><subject>Axotomy</subject><subject>Biomedical and Life Sciences</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>Female</subject><subject>Ganglia, Spinal - metabolism</subject><subject>Ganglia, Spinal - pathology</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nerve Regeneration</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteomics</subject><subject>Sciatic Nerve - metabolism</subject><subject>Sciatic Nerve - pathology</subject><subject>Sensory Receptor Cells - metabolism</subject><subject>Sensory Receptor Cells - pathology</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Spinal Cord Injuries - pathology</subject><issn>2522-5812</issn><issn>2522-5812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EolXpB7BBXrIJ-JXXsqp4iSJYwNpykklIldrFkyD69zhqQaxYWGPNvXMWh5Bzzq44k9k1KiHiOGKChReLSB6RaZgiijMujv_8J2SOuGaMCc4VF_kpmUiRplkm1ZRsFk8vj7R0tveuQ9q_AzVfzpqOemjAgjd9-xl2Rdu1_Y66mlbO4xg719PG2KZrDUWw6PyOWhi8s0hN3YOnuG1HUOl8RVu7HvzujJzUpkOYH-aMvN3evC7vo9Xz3cNysYpKFcs-SmLI8sKISiXSSJXWaSKUlDmvuDBJzeqE5yHNU5YxXqW1AiZknkJRmUSqLJEzcrnnbr37GAB7vWmxhK4zFtyAOtBEFivB41Dl-2rpHaKHWm99uzF-pznTo2i9F62DaD2K1jLcXBzwQ7GB6vfiR2soiH0BQ2Qb8HrtBh9k4D_UbxfCiLw</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Kong, Guiping</creator><creator>Zhou, Luming</creator><creator>Serger, Elisabeth</creator><creator>Palmisano, Ilaria</creator><creator>De Virgiliis, Francesco</creator><creator>Hutson, Thomas H.</creator><creator>Mclachlan, Eilidh</creator><creator>Freiwald, Anja</creator><creator>La Montanara, Paolo</creator><creator>Shkura, Kirill</creator><creator>Puttagunta, Radhika</creator><creator>Di Giovanni, Simone</creator><general>Nature Publishing Group UK</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3154-5399</orcidid><orcidid>https://orcid.org/0000-0002-7139-8090</orcidid><orcidid>https://orcid.org/0000-0002-1722-0910</orcidid><orcidid>https://orcid.org/0000-0001-7674-8064</orcidid><orcidid>https://orcid.org/0000-0001-6795-2688</orcidid></search><sort><creationdate>20200901</creationdate><title>AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury</title><author>Kong, Guiping ; Zhou, Luming ; Serger, Elisabeth ; Palmisano, Ilaria ; De Virgiliis, Francesco ; Hutson, Thomas H. ; Mclachlan, Eilidh ; Freiwald, Anja ; La Montanara, Paolo ; Shkura, Kirill ; Puttagunta, Radhika ; Di Giovanni, Simone</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-65e89ba2d463a347f76243391d12a6f0f619a2d970801d7f4e02397ebda634863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/89</topic><topic>14/19</topic><topic>42</topic><topic>42/44</topic><topic>45</topic><topic>45/91</topic><topic>631/378</topic><topic>631/443/319</topic><topic>631/80</topic><topic>64</topic><topic>64/60</topic><topic>82</topic><topic>82/58</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>ATPases Associated with Diverse Cellular Activities - metabolism</topic><topic>Axonal Transport</topic><topic>Axons</topic><topic>Axotomy</topic><topic>Biomedical and Life Sciences</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>Female</topic><topic>Ganglia, Spinal - metabolism</topic><topic>Ganglia, Spinal - pathology</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nerve Regeneration</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteomics</topic><topic>Sciatic Nerve - metabolism</topic><topic>Sciatic Nerve - pathology</topic><topic>Sensory Receptor Cells - metabolism</topic><topic>Sensory Receptor Cells - pathology</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>Spinal Cord Injuries - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kong, Guiping</creatorcontrib><creatorcontrib>Zhou, Luming</creatorcontrib><creatorcontrib>Serger, Elisabeth</creatorcontrib><creatorcontrib>Palmisano, Ilaria</creatorcontrib><creatorcontrib>De Virgiliis, Francesco</creatorcontrib><creatorcontrib>Hutson, Thomas H.</creatorcontrib><creatorcontrib>Mclachlan, Eilidh</creatorcontrib><creatorcontrib>Freiwald, Anja</creatorcontrib><creatorcontrib>La Montanara, Paolo</creatorcontrib><creatorcontrib>Shkura, Kirill</creatorcontrib><creatorcontrib>Puttagunta, Radhika</creatorcontrib><creatorcontrib>Di Giovanni, Simone</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nature metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kong, Guiping</au><au>Zhou, Luming</au><au>Serger, Elisabeth</au><au>Palmisano, Ilaria</au><au>De Virgiliis, Francesco</au><au>Hutson, Thomas H.</au><au>Mclachlan, Eilidh</au><au>Freiwald, Anja</au><au>La Montanara, Paolo</au><au>Shkura, Kirill</au><au>Puttagunta, Radhika</au><au>Di Giovanni, Simone</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury</atitle><jtitle>Nature metabolism</jtitle><stitle>Nat Metab</stitle><addtitle>Nat Metab</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>2</volume><issue>9</issue><spage>918</spage><epage>933</epage><pages>918-933</pages><issn>2522-5812</issn><eissn>2522-5812</eissn><abstract>Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Whereas peripheral axons regenerate well after injury, axons located in the central nervous system, such as in the spinal cord, do not. Kong et al. identify AMPK as a regulator of neuronal regeneration and show that deletion of AMPKα1 promotes regeneration of injured spinal cord axons in mice.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32778834</pmid><doi>10.1038/s42255-020-0252-3</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-3154-5399</orcidid><orcidid>https://orcid.org/0000-0002-7139-8090</orcidid><orcidid>https://orcid.org/0000-0002-1722-0910</orcidid><orcidid>https://orcid.org/0000-0001-7674-8064</orcidid><orcidid>https://orcid.org/0000-0001-6795-2688</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2522-5812 |
| ispartof | Nature metabolism, 2020-09, Vol.2 (9), p.918-933 |
| issn | 2522-5812 2522-5812 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2432854215 |
| source | MEDLINE; SpringerLink Journals |
| subjects | 13/89 14/19 42 42/44 45 45/91 631/378 631/443/319 631/80 64 64/60 82 82/58 AMP-Activated Protein Kinases - metabolism Animals ATPases Associated with Diverse Cellular Activities - metabolism Axonal Transport Axons Axotomy Biomedical and Life Sciences Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Female Ganglia, Spinal - metabolism Ganglia, Spinal - pathology Life Sciences Mice Mice, Inbred C57BL Nerve Regeneration Proteasome Endopeptidase Complex - metabolism Proteomics Sciatic Nerve - metabolism Sciatic Nerve - pathology Sensory Receptor Cells - metabolism Sensory Receptor Cells - pathology Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology |
| title | AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T02%3A47%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AMPK%20controls%20the%20axonal%20regenerative%20ability%20of%20dorsal%20root%20ganglia%20sensory%20neurons%20after%20spinal%20cord%20injury&rft.jtitle=Nature%20metabolism&rft.au=Kong,%20Guiping&rft.date=2020-09-01&rft.volume=2&rft.issue=9&rft.spage=918&rft.epage=933&rft.pages=918-933&rft.issn=2522-5812&rft.eissn=2522-5812&rft_id=info:doi/10.1038/s42255-020-0252-3&rft_dat=%3Cproquest_cross%3E2432854215%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2432854215&rft_id=info:pmid/32778834&rfr_iscdi=true |