Ellagic acid rescues motor and cognitive deficits in the R6/2 mouse model of Huntington's disease by lowering mutant huntingtin protein
Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggre...
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| Veröffentlicht in: | Food & function 2020-02, Vol.11 (2), p.1334-1348 |
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| creator | Sun, Xun Zhu, Jie Sun, Xiao-Ying Ji, Mei Yu, Xiao-Lin Liu, Rui-Tian |
| description | Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggregates of HTT, which leads to neuronal dysfunction and death. Therapies to lower mutant HTT (mHTT) and its aggregates appear to be the most promising strategies. Ellagic acid (EA) has been marketed as a dietary supplement with various claimed benefits and neuroprotective effects on several neurodegenerative disorders, while its effect on mHTT pathology is still unknown. Here we reported that EA significantly attenuated motor and cognitive deficits in R6/2 mice. Moreover, EA significantly lowered mHTT levels, reduced neuroinflammation, rescued synapse loss, and decreased oxidative stress in R6/2 mouse brains. These findings indicated that EA has promising therapeutic potential for HD treatment. |
| doi_str_mv | 10.1039/c9fo02131k |
| format | Article |
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These findings indicated that EA has promising therapeutic potential for HD treatment.</description><subject>Aggregates</subject><subject>Cognitive ability</subject><subject>Diet</subject><subject>Dietary supplements</subject><subject>Ellagic acid</subject><subject>Huntingtin</subject><subject>Huntington's disease</subject><subject>Huntingtons disease</subject><subject>Inflammation</subject><subject>Mutants</subject><subject>N-Terminus</subject><subject>Neurodegenerative diseases</subject><subject>Neuroprotection</subject><subject>Oligomers</subject><subject>Oxidative stress</subject><subject>Polyglutamine</subject><subject>Proteins</subject><subject>Trinucleotide repeat diseases</subject><subject>Trinucleotide repeats</subject><issn>2042-6496</issn><issn>2042-650X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNo9kN1KAzEQhYMoKtUbH0ACXghCbZLZv1xKUSsKgih4t2Szs23qNtEkq_QJfG2jVudiZuB8nGEOIUecnXMGcqJl55jgwF-2yL5gmRgXOXve_tszWeyRwxCWLBVIWclql-xBEiFnsE8-L_tezY2mSpuWegx6wEBXLjpPlW2pdnNronlH2mJntImBGkvjAulDMREJHAKm3mJPXUdng43GzqOzp4G2JqBKarOmvftAnwS6GqKykS42XLJ69S6isQdkp1N9wMPNHJGnq8vH6Wx8d399M724G2vIizhWUnIusGxKoUFhk1WyYU0HWKkKMOdYiUKWWdZhDq3IZSm1VHnLVAEZdsBhRE5-fdPdt_RqrJdu8DadrAUUUFWlKL6ps19KexeCx65-9Wal_LrmrP6OvZ7Kq_uf2G8TfLyxHJoVtv_oX8jwBXT3fko</recordid><startdate>20200226</startdate><enddate>20200226</enddate><creator>Sun, Xun</creator><creator>Zhu, Jie</creator><creator>Sun, Xiao-Ying</creator><creator>Ji, Mei</creator><creator>Yu, Xiao-Lin</creator><creator>Liu, Rui-Tian</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-4297-4765</orcidid></search><sort><creationdate>20200226</creationdate><title>Ellagic acid rescues motor and cognitive deficits in the R6/2 mouse model of Huntington's disease by lowering mutant huntingtin protein</title><author>Sun, Xun ; Zhu, Jie ; Sun, Xiao-Ying ; Ji, Mei ; Yu, Xiao-Lin ; Liu, Rui-Tian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-a99112e7b72c3aeb489b0bf3e8a83e51e8269744fe53d25979c9a5d0a634ef313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aggregates</topic><topic>Cognitive ability</topic><topic>Diet</topic><topic>Dietary supplements</topic><topic>Ellagic acid</topic><topic>Huntingtin</topic><topic>Huntington's disease</topic><topic>Huntingtons disease</topic><topic>Inflammation</topic><topic>Mutants</topic><topic>N-Terminus</topic><topic>Neurodegenerative diseases</topic><topic>Neuroprotection</topic><topic>Oligomers</topic><topic>Oxidative stress</topic><topic>Polyglutamine</topic><topic>Proteins</topic><topic>Trinucleotide repeat diseases</topic><topic>Trinucleotide repeats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Xun</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Sun, Xiao-Ying</creatorcontrib><creatorcontrib>Ji, Mei</creatorcontrib><creatorcontrib>Yu, Xiao-Lin</creatorcontrib><creatorcontrib>Liu, Rui-Tian</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Food & function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Xun</au><au>Zhu, Jie</au><au>Sun, Xiao-Ying</au><au>Ji, Mei</au><au>Yu, Xiao-Lin</au><au>Liu, Rui-Tian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ellagic acid rescues motor and cognitive deficits in the R6/2 mouse model of Huntington's disease by lowering mutant huntingtin protein</atitle><jtitle>Food & function</jtitle><addtitle>Food Funct</addtitle><date>2020-02-26</date><risdate>2020</risdate><volume>11</volume><issue>2</issue><spage>1334</spage><epage>1348</epage><pages>1334-1348</pages><issn>2042-6496</issn><eissn>2042-650X</eissn><abstract>Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggregates of HTT, which leads to neuronal dysfunction and death. Therapies to lower mutant HTT (mHTT) and its aggregates appear to be the most promising strategies. Ellagic acid (EA) has been marketed as a dietary supplement with various claimed benefits and neuroprotective effects on several neurodegenerative disorders, while its effect on mHTT pathology is still unknown. Here we reported that EA significantly attenuated motor and cognitive deficits in R6/2 mice. Moreover, EA significantly lowered mHTT levels, reduced neuroinflammation, rescued synapse loss, and decreased oxidative stress in R6/2 mouse brains. These findings indicated that EA has promising therapeutic potential for HD treatment.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>32043503</pmid><doi>10.1039/c9fo02131k</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-4297-4765</orcidid></addata></record> |
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| source | Royal Society Of Chemistry Journals 2008- |
| subjects | Aggregates Cognitive ability Diet Dietary supplements Ellagic acid Huntingtin Huntington's disease Huntingtons disease Inflammation Mutants N-Terminus Neurodegenerative diseases Neuroprotection Oligomers Oxidative stress Polyglutamine Proteins Trinucleotide repeat diseases Trinucleotide repeats |
| title | Ellagic acid rescues motor and cognitive deficits in the R6/2 mouse model of Huntington's disease by lowering mutant huntingtin protein |
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