Alpha synuclein is transported into and out of the brain by the blood–brain barrier
•Alpha-synuclein crosses the blood–brain barrier in both the blood-to-brain and the brain-to-blood direction.•Inflammation as induced by lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption. Alpha-synuclein (α-Syn), a small protein with multiple physiolog...
Gespeichert in:
| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2014-12, Vol.62, p.197-202 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 202 |
|---|---|
| container_issue | |
| container_start_page | 197 |
| container_title | Peptides (New York, N.Y. : 1980) |
| container_volume | 62 |
| creator | Sui, Yu-Ting Bullock, Kristin M. Erickson, Michelle A. Zhang, Jing Banks, W.A. |
| description | •Alpha-synuclein crosses the blood–brain barrier in both the blood-to-brain and the brain-to-blood direction.•Inflammation as induced by lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption.
Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood–brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB. |
| doi_str_mv | 10.1016/j.peptides.2014.09.018 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4378645</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0196978114002873</els_id><sourcerecordid>1651438041</sourcerecordid><originalsourceid>FETCH-LOGICAL-c537t-f817d71c4ccc6be9e76df578f9589143b25d6cc204738c9a22e0893f0439e20a3</originalsourceid><addsrcrecordid>eNqFkc1u1DAUhS0EokPhFaos2ST4_2eDqCpokSqxoWvLsW8YjzJxsJNKs-MdeEOeBFczrWDV1ZWvv3t8fA9CFwR3BBP5YdfNMC8xQOkoJrzDpsNEv0AbohVrBZHmJdpgYmRrlCZn6E0pO4wx50a_RmdUUKW5oRt0dznOW9eUw7T6EeLUxNIs2U1lTnmB0MRpSY2bQpPWpUlDs2yh6bOrYH84HsaUwp9fv09Nl3OE_Ba9GtxY4N2pnqO7L5-_X920t9-uv15d3rZeMLW0gyYqKOK59172YEDJMAilByO0IZz1VATpPcVcMe2NoxSwNmzAnBmg2LFz9PGoO6_9HoKHqXof7Zzj3uWDTS7a_2-muLU_0r3lTGnJRRV4fxLI6ecKZbH7WDyMo5sgrcUSJRhXRAr2PCpFtawxJxWVR9TnVEqG4ckRwfYhPruzj_HZh_gsNrbGVwcv_v3P09hjXhX4dASgbvW-btoWH2HyEGIGv9iQ4nNv_AVSqLFF</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1651438041</pqid></control><display><type>article</type><title>Alpha synuclein is transported into and out of the brain by the blood–brain barrier</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Sui, Yu-Ting ; Bullock, Kristin M. ; Erickson, Michelle A. ; Zhang, Jing ; Banks, W.A.</creator><creatorcontrib>Sui, Yu-Ting ; Bullock, Kristin M. ; Erickson, Michelle A. ; Zhang, Jing ; Banks, W.A.</creatorcontrib><description>•Alpha-synuclein crosses the blood–brain barrier in both the blood-to-brain and the brain-to-blood direction.•Inflammation as induced by lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption.
Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood–brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2014.09.018</identifier><identifier>PMID: 25278492</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alpha-synuclein ; alpha-Synuclein - metabolism ; Animals ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Biological Transport ; Biomedical materials ; Blood ; Blood-brain barrier ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - physiology ; Brain ; Central nervous system ; Efflux ; Humans ; Inflammation - chemically induced ; Inflammation - mortality ; Inflammation - pathology ; Lewy Bodies - metabolism ; Lewy Bodies - pathology ; Lipopolysaccharides - toxicity ; Lipoproteins, LDL ; Low Density Lipoprotein Receptor-Related Protein-1 ; LRP-1 ; Mice ; p-Glycoprotein ; Parkinson Disease - metabolism ; Parkinson Disease - physiopathology ; Parkinson's disease ; Proteins ; Receptors, LDL - metabolism ; Tumor Suppressor Proteins - metabolism ; Uptakes</subject><ispartof>Peptides (New York, N.Y. : 1980), 2014-12, Vol.62, p.197-202</ispartof><rights>2014</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-f817d71c4ccc6be9e76df578f9589143b25d6cc204738c9a22e0893f0439e20a3</citedby><cites>FETCH-LOGICAL-c537t-f817d71c4ccc6be9e76df578f9589143b25d6cc204738c9a22e0893f0439e20a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.peptides.2014.09.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25278492$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sui, Yu-Ting</creatorcontrib><creatorcontrib>Bullock, Kristin M.</creatorcontrib><creatorcontrib>Erickson, Michelle A.</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Banks, W.A.</creatorcontrib><title>Alpha synuclein is transported into and out of the brain by the blood–brain barrier</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>•Alpha-synuclein crosses the blood–brain barrier in both the blood-to-brain and the brain-to-blood direction.•Inflammation as induced by lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption.
Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood–brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.</description><subject>Alpha-synuclein</subject><subject>alpha-Synuclein - metabolism</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Biological Transport</subject><subject>Biomedical materials</subject><subject>Blood</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blood-Brain Barrier - physiology</subject><subject>Brain</subject><subject>Central nervous system</subject><subject>Efflux</subject><subject>Humans</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - mortality</subject><subject>Inflammation - pathology</subject><subject>Lewy Bodies - metabolism</subject><subject>Lewy Bodies - pathology</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Lipoproteins, LDL</subject><subject>Low Density Lipoprotein Receptor-Related Protein-1</subject><subject>LRP-1</subject><subject>Mice</subject><subject>p-Glycoprotein</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson Disease - physiopathology</subject><subject>Parkinson's disease</subject><subject>Proteins</subject><subject>Receptors, LDL - metabolism</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Uptakes</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EokPhFaos2ST4_2eDqCpokSqxoWvLsW8YjzJxsJNKs-MdeEOeBFczrWDV1ZWvv3t8fA9CFwR3BBP5YdfNMC8xQOkoJrzDpsNEv0AbohVrBZHmJdpgYmRrlCZn6E0pO4wx50a_RmdUUKW5oRt0dznOW9eUw7T6EeLUxNIs2U1lTnmB0MRpSY2bQpPWpUlDs2yh6bOrYH84HsaUwp9fv09Nl3OE_Ba9GtxY4N2pnqO7L5-_X920t9-uv15d3rZeMLW0gyYqKOK59172YEDJMAilByO0IZz1VATpPcVcMe2NoxSwNmzAnBmg2LFz9PGoO6_9HoKHqXof7Zzj3uWDTS7a_2-muLU_0r3lTGnJRRV4fxLI6ecKZbH7WDyMo5sgrcUSJRhXRAr2PCpFtawxJxWVR9TnVEqG4ckRwfYhPruzj_HZh_gsNrbGVwcv_v3P09hjXhX4dASgbvW-btoWH2HyEGIGv9iQ4nNv_AVSqLFF</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Sui, Yu-Ting</creator><creator>Bullock, Kristin M.</creator><creator>Erickson, Michelle A.</creator><creator>Zhang, Jing</creator><creator>Banks, W.A.</creator><general>Elsevier Inc</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>7U5</scope><scope>8FD</scope><scope>L7M</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20141201</creationdate><title>Alpha synuclein is transported into and out of the brain by the blood–brain barrier</title><author>Sui, Yu-Ting ; Bullock, Kristin M. ; Erickson, Michelle A. ; Zhang, Jing ; Banks, W.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-f817d71c4ccc6be9e76df578f9589143b25d6cc204738c9a22e0893f0439e20a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alpha-synuclein</topic><topic>alpha-Synuclein - metabolism</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Biological Transport</topic><topic>Biomedical materials</topic><topic>Blood</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blood-Brain Barrier - physiology</topic><topic>Brain</topic><topic>Central nervous system</topic><topic>Efflux</topic><topic>Humans</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - mortality</topic><topic>Inflammation - pathology</topic><topic>Lewy Bodies - metabolism</topic><topic>Lewy Bodies - pathology</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Lipoproteins, LDL</topic><topic>Low Density Lipoprotein Receptor-Related Protein-1</topic><topic>LRP-1</topic><topic>Mice</topic><topic>p-Glycoprotein</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - physiopathology</topic><topic>Parkinson's disease</topic><topic>Proteins</topic><topic>Receptors, LDL - metabolism</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Uptakes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sui, Yu-Ting</creatorcontrib><creatorcontrib>Bullock, Kristin M.</creatorcontrib><creatorcontrib>Erickson, Michelle A.</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Banks, W.A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sui, Yu-Ting</au><au>Bullock, Kristin M.</au><au>Erickson, Michelle A.</au><au>Zhang, Jing</au><au>Banks, W.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha synuclein is transported into and out of the brain by the blood–brain barrier</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>62</volume><spage>197</spage><epage>202</epage><pages>197-202</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract>•Alpha-synuclein crosses the blood–brain barrier in both the blood-to-brain and the brain-to-blood direction.•Inflammation as induced by lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption.
Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood–brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25278492</pmid><doi>10.1016/j.peptides.2014.09.018</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0196-9781 |
| ispartof | Peptides (New York, N.Y. : 1980), 2014-12, Vol.62, p.197-202 |
| issn | 0196-9781 1873-5169 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4378645 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Alpha-synuclein alpha-Synuclein - metabolism Animals ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Biological Transport Biomedical materials Blood Blood-brain barrier Blood-Brain Barrier - metabolism Blood-Brain Barrier - physiology Brain Central nervous system Efflux Humans Inflammation - chemically induced Inflammation - mortality Inflammation - pathology Lewy Bodies - metabolism Lewy Bodies - pathology Lipopolysaccharides - toxicity Lipoproteins, LDL Low Density Lipoprotein Receptor-Related Protein-1 LRP-1 Mice p-Glycoprotein Parkinson Disease - metabolism Parkinson Disease - physiopathology Parkinson's disease Proteins Receptors, LDL - metabolism Tumor Suppressor Proteins - metabolism Uptakes |
| title | Alpha synuclein is transported into and out of the brain by the blood–brain barrier |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T02%3A51%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alpha%20synuclein%20is%20transported%20into%20and%20out%20of%20the%20brain%20by%20the%20blood%E2%80%93brain%20barrier&rft.jtitle=Peptides%20(New%20York,%20N.Y.%20:%201980)&rft.au=Sui,%20Yu-Ting&rft.date=2014-12-01&rft.volume=62&rft.spage=197&rft.epage=202&rft.pages=197-202&rft.issn=0196-9781&rft.eissn=1873-5169&rft_id=info:doi/10.1016/j.peptides.2014.09.018&rft_dat=%3Cproquest_pubme%3E1651438041%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1651438041&rft_id=info:pmid/25278492&rft_els_id=S0196978114002873&rfr_iscdi=true |