Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains
Abstract Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despi...
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2020-08, Vol.79 (8), p.902-907 |
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| container_title | Journal of neuropathology and experimental neurology |
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| creator | Verheijen, Bert M Morimoto, Satoru Sasaki, Ryogen Oyanagi, Kiyomitsu Kokubo, Yasumasa Kuzuhara, Shigeki van Leeuwen, Fred W |
| description | Abstract
Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC. |
| doi_str_mv | 10.1093/jnen/nlaa056 |
| format | Article |
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Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlaa056</identifier><identifier>PMID: 32647880</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - genetics ; Amyotrophic Lateral Sclerosis - metabolism ; Amyotrophic Lateral Sclerosis - pathology ; Brain - metabolism ; Brain - pathology ; Brain diseases ; Brain research ; Dementia ; Development and progression ; Endemic diseases ; Frameshift Mutation ; Gene mutations ; Genetic aspects ; Health aspects ; Homeostasis ; Humans ; Japan ; Parkinsonism ; Protein metabolism disorders ; Proteins ; Proteostasis - genetics ; Proteostasis Deficiencies - genetics ; Proteostasis Deficiencies - metabolism ; Proteostasis Deficiencies - pathology ; Ubiquitin ; Ubiquitin - genetics</subject><ispartof>Journal of neuropathology and experimental neurology, 2020-08, Vol.79 (8), p.902-907</ispartof><rights>2020 American Association of Neuropathologists, Inc. 2020</rights><rights>2020 by American Association of Neuropathologists, Inc.</rights><rights>2020 American Association of Neuropathologists, Inc.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5679-91234202709ea816214980049debe5390c6db0c460258577b98c25982ba0ddac3</citedby><cites>FETCH-LOGICAL-c5679-91234202709ea816214980049debe5390c6db0c460258577b98c25982ba0ddac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1583,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32647880$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verheijen, Bert M</creatorcontrib><creatorcontrib>Morimoto, Satoru</creatorcontrib><creatorcontrib>Sasaki, Ryogen</creatorcontrib><creatorcontrib>Oyanagi, Kiyomitsu</creatorcontrib><creatorcontrib>Kokubo, Yasumasa</creatorcontrib><creatorcontrib>Kuzuhara, Shigeki</creatorcontrib><creatorcontrib>van Leeuwen, Fred W</creatorcontrib><title>Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Abstract
Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Amyotrophic Lateral Sclerosis - metabolism</subject><subject>Amyotrophic Lateral Sclerosis - pathology</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain diseases</subject><subject>Brain research</subject><subject>Dementia</subject><subject>Development and progression</subject><subject>Endemic diseases</subject><subject>Frameshift Mutation</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Japan</subject><subject>Parkinsonism</subject><subject>Protein metabolism disorders</subject><subject>Proteins</subject><subject>Proteostasis - genetics</subject><subject>Proteostasis Deficiencies - genetics</subject><subject>Proteostasis Deficiencies - metabolism</subject><subject>Proteostasis Deficiencies - pathology</subject><subject>Ubiquitin</subject><subject>Ubiquitin - genetics</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><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>eNp9kkFv1DAQhSMEokvhxhlZ4gAH0p3YSRwft0uBikVUgp4tx5llvXXs1E7U9t4fXq92AYEQ8sHyzPdGT_OcZS8LOClAsPnWoZs7qxRU9aNsVlRVmdcVbx5nMwBKcwa1OMqexbgFAAGifJodMVqXvGlglt2f3Q4BYzTeEb8mX6ZRuZFctuZ6MqNxRLmOXAQ_oo-jiiaS835QJvSYqNT-bAxZ9Hd-DH7YGE1WasSgLPmmLQaf-PmFClfGRe9M7PP3uBMaRZa-HyzektOgUvN59mStbMQXh_s4u_xw9n35KV99_Xi-XKxyXdVc5KKgrKRAOQhUTVHTohQNQCk6bLFiAnTdtaDLGmjVVJy3otG0Eg1tFXSd0uw4e7ufOwR_PWEcZW-iRmuVQz9FSUuatsVYUyb09V_o1k_BJXeJ4oxz2jD2m_qhLErj1mkRSu-GygUHSHMKUSfq5B9UOh32RnuHa5Pqfwje7QU67TAGXMshmF6FO1mA3IUud6HLQ-gJf3XwOrU9dr_gnyknoNwDN96mfOKVnW4wyA0qO25k-hZQAad5Wm2ykF75riSS7M1e5qfh_w4eAAIaxT0</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Verheijen, Bert M</creator><creator>Morimoto, Satoru</creator><creator>Sasaki, Ryogen</creator><creator>Oyanagi, Kiyomitsu</creator><creator>Kokubo, Yasumasa</creator><creator>Kuzuhara, Shigeki</creator><creator>van Leeuwen, Fred W</creator><general>Oxford University Press</general><general>by American Association of Neuropathologists, Inc</general><scope>TOX</scope><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20200801</creationdate><title>Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains</title><author>Verheijen, Bert M ; Morimoto, Satoru ; Sasaki, Ryogen ; Oyanagi, Kiyomitsu ; Kokubo, Yasumasa ; Kuzuhara, Shigeki ; van Leeuwen, Fred W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5679-91234202709ea816214980049debe5390c6db0c460258577b98c25982ba0ddac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Amyotrophic lateral sclerosis</topic><topic>Amyotrophic Lateral Sclerosis - genetics</topic><topic>Amyotrophic Lateral Sclerosis - metabolism</topic><topic>Amyotrophic Lateral Sclerosis - pathology</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain diseases</topic><topic>Brain research</topic><topic>Dementia</topic><topic>Development and progression</topic><topic>Endemic diseases</topic><topic>Frameshift Mutation</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Japan</topic><topic>Parkinsonism</topic><topic>Protein metabolism disorders</topic><topic>Proteins</topic><topic>Proteostasis - genetics</topic><topic>Proteostasis Deficiencies - genetics</topic><topic>Proteostasis Deficiencies - metabolism</topic><topic>Proteostasis Deficiencies - pathology</topic><topic>Ubiquitin</topic><topic>Ubiquitin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verheijen, Bert M</creatorcontrib><creatorcontrib>Morimoto, Satoru</creatorcontrib><creatorcontrib>Sasaki, Ryogen</creatorcontrib><creatorcontrib>Oyanagi, Kiyomitsu</creatorcontrib><creatorcontrib>Kokubo, Yasumasa</creatorcontrib><creatorcontrib>Kuzuhara, Shigeki</creatorcontrib><creatorcontrib>van Leeuwen, Fred W</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</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>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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</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 Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verheijen, Bert M</au><au>Morimoto, Satoru</au><au>Sasaki, Ryogen</au><au>Oyanagi, Kiyomitsu</au><au>Kokubo, Yasumasa</au><au>Kuzuhara, Shigeki</au><au>van Leeuwen, Fred W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>79</volume><issue>8</issue><spage>902</spage><epage>907</epage><pages>902-907</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>Abstract
Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32647880</pmid><doi>10.1093/jnen/nlaa056</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Amyotrophic Lateral Sclerosis - metabolism Amyotrophic Lateral Sclerosis - pathology Brain - metabolism Brain - pathology Brain diseases Brain research Dementia Development and progression Endemic diseases Frameshift Mutation Gene mutations Genetic aspects Health aspects Homeostasis Humans Japan Parkinsonism Protein metabolism disorders Proteins Proteostasis - genetics Proteostasis Deficiencies - genetics Proteostasis Deficiencies - metabolism Proteostasis Deficiencies - pathology Ubiquitin Ubiquitin - genetics |
| title | Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains |
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