Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α
Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal dea...
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Veröffentlicht in: | The Journal of cell biology 2001-10, Vol.155 (2), p.217-226 |
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description | Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal death, we analyzed the effects of peripherin overexpression in primary neuronal cultures. Peripherin overexpression led to the formation of cytoplasmic protein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated spinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons containing peripherin aggregates was dependent on the proinflammatory central nervous system environment of spinal cultures, rich in activated microglia, and required TNF-α. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS. |
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To further clarify the selectivity and mechanism of peripherin-induced neuronal death, we analyzed the effects of peripherin overexpression in primary neuronal cultures. Peripherin overexpression led to the formation of cytoplasmic protein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated spinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons containing peripherin aggregates was dependent on the proinflammatory central nervous system environment of spinal cultures, rich in activated microglia, and required TNF-α. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200107058</identifier><identifier>PMID: 11604419</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - pathology ; Animals ; Antibodies ; Antibodies - pharmacology ; Apoptosis ; Cell aggregates ; Cells, Cultured ; Cellular biology ; Cultured cells ; Cytokines ; Ganglia, Spinal - ultrastructure ; Intermediate Filament Proteins - genetics ; Intermediate Filament Proteins - ultrastructure ; Membrane Glycoproteins ; Mice ; Mice, Transgenic ; Microglia ; Microglia - metabolism ; Microinjections ; Motor neurons ; Motor Neurons - ultrastructure ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - ultrastructure ; Neurons ; Peripherins ; Proteins ; Spinal cord ; Spinal Cord - physiology ; Transgenic animals ; Tumor Necrosis Factor-alpha - immunology ; Tumor Necrosis Factor-alpha - physiology ; Tumors</subject><ispartof>The Journal of cell biology, 2001-10, Vol.155 (2), p.217-226</ispartof><rights>Copyright 2001 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press Oct 15, 2001</rights><rights>Copyright © 2001, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-5943c280342fdb860e57e7b8c9d33e9b76d54e6972abef35c232eef4ccc7a2603</citedby><cites>FETCH-LOGICAL-c431t-5943c280342fdb860e57e7b8c9d33e9b76d54e6972abef35c232eef4ccc7a2603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11604419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robertson, Janice</creatorcontrib><creatorcontrib>Beaulieu, Jean-Martin</creatorcontrib><creatorcontrib>Doroudchi, Mohammad M.</creatorcontrib><creatorcontrib>Durham, Heather D.</creatorcontrib><creatorcontrib>Julien, Jean-Pierre</creatorcontrib><creatorcontrib>Mushynski, Walter E.</creatorcontrib><title>Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal death, we analyzed the effects of peripherin overexpression in primary neuronal cultures. Peripherin overexpression led to the formation of cytoplasmic protein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated spinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons containing peripherin aggregates was dependent on the proinflammatory central nervous system environment of spinal cultures, rich in activated microglia, and required TNF-α. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - pathology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - pharmacology</subject><subject>Apoptosis</subject><subject>Cell aggregates</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cultured cells</subject><subject>Cytokines</subject><subject>Ganglia, Spinal - ultrastructure</subject><subject>Intermediate Filament Proteins - genetics</subject><subject>Intermediate Filament Proteins - ultrastructure</subject><subject>Membrane Glycoproteins</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microglia</subject><subject>Microglia - metabolism</subject><subject>Microinjections</subject><subject>Motor neurons</subject><subject>Motor Neurons - ultrastructure</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - ultrastructure</subject><subject>Neurons</subject><subject>Peripherins</subject><subject>Proteins</subject><subject>Spinal cord</subject><subject>Spinal Cord - physiology</subject><subject>Transgenic animals</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><subject>Tumors</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAURiMEokNhyQ4hi0V3Kdc_iZMN0mhooVKBLso6cpybxEMSB9tBnR2vxIvwTHg0oxbY2Ja-o6Pr-yXJSwrnFAr-dqvrcwZAQUJWPEpWNBOQFlTA42QFwGhaZiw7SZ55vwUAIQV_mpxQmoMQtFwlP9eznYMNRpP3qEJPbEs-4-Ls5MnFXW9qE8zUkRt0Zu7jMZF11znsVEBPrjz5hI2J74bUOxJ6JDfOmqkd1DiqYN2ObHbBfjMTkttltC6qtbPeeHKpdMzT37-eJ09aNXh8cbxPk6-XF7ebj-n1lw9Xm_V1qgWnIc1KwTUrgAvWNnWRA2YSZV3osuEcy1rmTSYwLyVTNbY804wzxFZoraViOfDT5N3BOy_1iI3GKTg1VLMzo3K7yipT_ZtMpq86-6NitCwKsRecHQXOfl_Qh2o0XuMwqAnt4ivJGIiMygi--Q_c2sVN8XPRJaFkZUEjlB6g_T68w_Z-EgrVvtgqFlvdFxv513-P_0Afm4zAqwOw9XGxD3nOQPKS_wHIEask</recordid><startdate>20011015</startdate><enddate>20011015</enddate><creator>Robertson, Janice</creator><creator>Beaulieu, Jean-Martin</creator><creator>Doroudchi, Mohammad M.</creator><creator>Durham, Heather D.</creator><creator>Julien, Jean-Pierre</creator><creator>Mushynski, Walter E.</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20011015</creationdate><title>Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α</title><author>Robertson, Janice ; 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subjects | Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - pathology Animals Antibodies Antibodies - pharmacology Apoptosis Cell aggregates Cells, Cultured Cellular biology Cultured cells Cytokines Ganglia, Spinal - ultrastructure Intermediate Filament Proteins - genetics Intermediate Filament Proteins - ultrastructure Membrane Glycoproteins Mice Mice, Transgenic Microglia Microglia - metabolism Microinjections Motor neurons Motor Neurons - ultrastructure Nerve Tissue Proteins - genetics Nerve Tissue Proteins - ultrastructure Neurons Peripherins Proteins Spinal cord Spinal Cord - physiology Transgenic animals Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - physiology Tumors |
title | Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α |
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