Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activation
α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18...
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| Veröffentlicht in: | Metabolic brain disease 2022-06, Vol.37 (5), p.1669-1681 |
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| creator | Hu, Qi Hong, Mei Huang, Mengyang Gong, Quan Zhang, Xiaofan Uversky, Vladimir N. Pan-Montojo, Francisco Huang, Teng Zhou, Honglian Zhu, Suiqiang |
| description | α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation. |
| doi_str_mv | 10.1007/s11011-022-00917-6 |
| format | Article |
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As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation.</description><identifier>ISSN: 0885-7490</identifier><identifier>EISSN: 1573-7365</identifier><identifier>DOI: 10.1007/s11011-022-00917-6</identifier><identifier>PMID: 35089485</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Agglomeration ; Aging ; alpha-Synuclein - metabolism ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain-Gut Axis ; Caspase 1 - metabolism ; Caspase-1 ; Caspases - metabolism ; Dopamine ; Hydroxylase ; Ileum ; Mesencephalon ; Mesencephalon - metabolism ; Metabolic Diseases ; Mice ; Monomers ; Movement disorders ; mRNA ; Nervous system ; Neurodegenerative diseases ; Neurology ; Neurosciences ; Oligomers ; Oncology ; Original Article ; Parkinson Disease - metabolism ; Parkinson's disease ; Risk analysis ; Risk factors ; Rotenone ; Small intestine ; Spinal cord ; Synuclein ; Thorax ; Tyrosine ; Tyrosine 3-monooxygenase</subject><ispartof>Metabolic brain disease, 2022-06, Vol.37 (5), p.1669-1681</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-44bf67d114af0ba4a5ff44e595737506c7175fc465ceee80f91ffdbf97ede6a13</citedby><cites>FETCH-LOGICAL-c419t-44bf67d114af0ba4a5ff44e595737506c7175fc465ceee80f91ffdbf97ede6a13</cites><orcidid>0000-0003-1025-164X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11011-022-00917-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11011-022-00917-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35089485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Qi</creatorcontrib><creatorcontrib>Hong, Mei</creatorcontrib><creatorcontrib>Huang, Mengyang</creatorcontrib><creatorcontrib>Gong, Quan</creatorcontrib><creatorcontrib>Zhang, Xiaofan</creatorcontrib><creatorcontrib>Uversky, Vladimir N.</creatorcontrib><creatorcontrib>Pan-Montojo, Francisco</creatorcontrib><creatorcontrib>Huang, Teng</creatorcontrib><creatorcontrib>Zhou, Honglian</creatorcontrib><creatorcontrib>Zhu, Suiqiang</creatorcontrib><title>Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activation</title><title>Metabolic brain disease</title><addtitle>Metab Brain Dis</addtitle><addtitle>Metab Brain Dis</addtitle><description>α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation.</description><subject>Agglomeration</subject><subject>Aging</subject><subject>alpha-Synuclein - metabolism</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain-Gut Axis</subject><subject>Caspase 1 - metabolism</subject><subject>Caspase-1</subject><subject>Caspases - metabolism</subject><subject>Dopamine</subject><subject>Hydroxylase</subject><subject>Ileum</subject><subject>Mesencephalon</subject><subject>Mesencephalon - metabolism</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Monomers</subject><subject>Movement disorders</subject><subject>mRNA</subject><subject>Nervous system</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Oligomers</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson's disease</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Rotenone</subject><subject>Small intestine</subject><subject>Spinal cord</subject><subject>Synuclein</subject><subject>Thorax</subject><subject>Tyrosine</subject><subject>Tyrosine 3-monooxygenase</subject><issn>0885-7490</issn><issn>1573-7365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAQxy0EokvhBTggS1y4GDyJP5JjVfElVeICZ8txxmmqXWfxOIV9LF6EZ8LbLSBxQBrJh_nN3x7_GHsO8jVIad8QgAQQsmmElD1YYR6wDWjbCtsa_ZBtZNdpYVUvz9gTohspZauhf8zOWi27XnV6ww4XE4oR95hGTIX7aco4-TIviS-R__wh6JDWsMU58VrlGnnCfLusxOlABXdHalqLGLKvff99Jl7LEy1h9gVH_m0u1zx42ntCAdyHMt_e5T9lj6LfEj67P8_Zl3dvP19-EFef3n-8vLgSQUFfhFJDNHYEUD7KwSuvY1QKdV_3tFqaYMHqGJTRARE7GXuIcRxib3FE46E9Z69Oufu8fF2RitvNFHC79QnrHq4xTdv1bdMc0Zf_oDfLmlN9XaWMgQbqX1aqOVEhL0QZo9vneefzwYF0RzHuJMZVMe5OjDN16MV99DrscPwz8ttEBdoTQLWVJsx_7_5P7C-JjZrY</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Hu, Qi</creator><creator>Hong, Mei</creator><creator>Huang, Mengyang</creator><creator>Gong, Quan</creator><creator>Zhang, Xiaofan</creator><creator>Uversky, Vladimir N.</creator><creator>Pan-Montojo, Francisco</creator><creator>Huang, Teng</creator><creator>Zhou, Honglian</creator><creator>Zhu, Suiqiang</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1025-164X</orcidid></search><sort><creationdate>20220601</creationdate><title>Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activation</title><author>Hu, Qi ; Hong, Mei ; Huang, Mengyang ; Gong, Quan ; Zhang, Xiaofan ; Uversky, Vladimir N. ; Pan-Montojo, Francisco ; Huang, Teng ; Zhou, Honglian ; Zhu, Suiqiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-44bf67d114af0ba4a5ff44e595737506c7175fc465ceee80f91ffdbf97ede6a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Agglomeration</topic><topic>Aging</topic><topic>alpha-Synuclein - metabolism</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain-Gut Axis</topic><topic>Caspase 1 - metabolism</topic><topic>Caspase-1</topic><topic>Caspases - metabolism</topic><topic>Dopamine</topic><topic>Hydroxylase</topic><topic>Ileum</topic><topic>Mesencephalon</topic><topic>Mesencephalon - metabolism</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Monomers</topic><topic>Movement disorders</topic><topic>mRNA</topic><topic>Nervous system</topic><topic>Neurodegenerative diseases</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Oligomers</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson's disease</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Rotenone</topic><topic>Small intestine</topic><topic>Spinal cord</topic><topic>Synuclein</topic><topic>Thorax</topic><topic>Tyrosine</topic><topic>Tyrosine 3-monooxygenase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Qi</creatorcontrib><creatorcontrib>Hong, Mei</creatorcontrib><creatorcontrib>Huang, Mengyang</creatorcontrib><creatorcontrib>Gong, Quan</creatorcontrib><creatorcontrib>Zhang, Xiaofan</creatorcontrib><creatorcontrib>Uversky, Vladimir N.</creatorcontrib><creatorcontrib>Pan-Montojo, Francisco</creatorcontrib><creatorcontrib>Huang, Teng</creatorcontrib><creatorcontrib>Zhou, Honglian</creatorcontrib><creatorcontrib>Zhu, Suiqiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolic brain disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Qi</au><au>Hong, Mei</au><au>Huang, Mengyang</au><au>Gong, Quan</au><au>Zhang, Xiaofan</au><au>Uversky, Vladimir N.</au><au>Pan-Montojo, Francisco</au><au>Huang, Teng</au><au>Zhou, Honglian</au><au>Zhu, Suiqiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activation</atitle><jtitle>Metabolic brain disease</jtitle><stitle>Metab Brain Dis</stitle><addtitle>Metab Brain Dis</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>37</volume><issue>5</issue><spage>1669</spage><epage>1681</epage><pages>1669-1681</pages><issn>0885-7490</issn><eissn>1573-7365</eissn><abstract>α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35089485</pmid><doi>10.1007/s11011-022-00917-6</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-1025-164X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Agglomeration Aging alpha-Synuclein - metabolism Animals Biochemistry Biomedical and Life Sciences Biomedicine Brain Brain-Gut Axis Caspase 1 - metabolism Caspase-1 Caspases - metabolism Dopamine Hydroxylase Ileum Mesencephalon Mesencephalon - metabolism Metabolic Diseases Mice Monomers Movement disorders mRNA Nervous system Neurodegenerative diseases Neurology Neurosciences Oligomers Oncology Original Article Parkinson Disease - metabolism Parkinson's disease Risk analysis Risk factors Rotenone Small intestine Spinal cord Synuclein Thorax Tyrosine Tyrosine 3-monooxygenase |
| title | Age-dependent aggregation of α-synuclein in the nervous system of gut-brain axis is associated with caspase-1 activation |
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