JP7062660B2 - 全体的な翻訳の減少に基づくパーキンソン病の診断 - Google Patents
全体的な翻訳の減少に基づくパーキンソン病の診断 Download PDFInfo
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Description
すべての患者試料は、トゥルク大学およびNINDSリポジトリ(米国)から、倫理的ガイドラインに従って適切な許可およびインフォームドコンセントを得て入手した。
Claims (15)
- 対象におけるパーキンソン病(PD)の診断の補助またはモニタリングをする方法であって、全体的な翻訳レベルの変化について、対象から得られた試料を試験することを含み、全体的な翻訳の減少がPDを示し、
SNX2及び/又はLIMA1発現の減少を全体的な翻訳の減少の指標とし、
更に、以下の発現シグネチャのグループ(1)~(3):
(1)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1LおよびRPL27、
(2)RASA1MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167AおよびASNS、ならびに
(3)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1L、RPL27、MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、RA-SA1、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167A、ASNS、FAM120A、ADAR、MAP1A、COL5A、BCL9L、USP7、RECK、CNOT7、NKIRAS1、ARPC5、CPN31、TMEM208、CRIP2、GDI1、USP9X、ADRM1、PEF1、YIF1B、GHITM、CANX、TNS1、OGDH、TNPO1、PEPD、HNRNFA3、MAP4、ALDH18A1、DDX21、DERL1、TPM2、NPM1、CLIC4、HLA-A、CDC41、STT3A、RHOA、CTNNB1、TRAM1、PLS3、SSR3、CTSK、NCBP1、PTRH2、SLC35B2、SF3B3、SLC2A14、SLC2A3、NUCB2、HEL-S-109、SEC61G、CLPTM1、PRMT1、ABCF2、VAMP7、RTCA、AEBP1、CPXM2、S100A16、RRAGD、RRAGC、EHD1、PALLD、CERS2、RPL17、RTN1、RAB8B、RPS15A、PYCR1、RAB5A、LOX、SEC61B、RPL36AL、PAWRおよびAPOL6から選択される遺伝子によりコードされる1種または複数のタンパク質
から選択される少なくとも1つのグループを、全体的な翻訳の減少の指標とする、方法。 - 前記PDが孤発性PDである、請求項1に記載の方法。
- 前記グループ(3)は、FAM120A、ADAR、MAP1A、COL5A、BCL9L、USP7、RECK、CNOT7、NKIRAS1、ARPC5、CPN31、TMEM208、CRIP2、GDI1、USP9X、ADRM1、PEF1、YIF1B、CANX、GHITM、CANX、TNS1、OGDH、TNPO1 PEPD、HNRNFA3、MAP4、ALDH18A1、DDX21、DERL1、TPM2、NPM1、CLIC4、HLA-A、CDC41、STT3A、RHOA、CTNNB1、TRAM1、PLS3、SSR3、CTSK、NCBP1、PTRH2、SLC35B2、SF3B3、SLC2A14、SLC2A3、NUCB2、HEL-S-109、SEC61G、CLPTM1、RECK、PRMT1、ABCF2、VAMP7、RTCA、AEBP1、CPXM2、S100A16、RRAGD、RRAGC、EHD1、PALLD、PSMC1、CERS2、RPL17、RTN1、RAB8B、RPS15A、PYCR1、RAB5A、LOX、HNRNPA3、SEC61B、RPL36AL、PAWRおよびAPOL6からなる群から選択された遺伝子によりコードされる1種または複数のタンパク質を含む、請求項1に記載の方法。
- 前記対象が、G2019Sのキャリアであるか、または孤発性PD患者のサブグループに属する、請求項3に記載の方法。
- 対照試料と比較した際の翻訳の変化レベルが、全体的な翻訳の減少を示す、請求項1から4のいずれか一項に記載の方法。
- 翻訳レベルが、選択反応モニタリング(SRM)、多重反応モニタリング(MRM)、並行反応モニタリング(PRM)、データ依存型取得(DDA)またはデータ非依存型取得(DIA)を含む質量分析、代謝標識およびクリックケミストリーからなる群から選択される方法によって評価される抗体をベースとする方法である、請求項1から5のいずれか一項に記載の方法。
- 質量分析法または抗体によって定量的または定性的に評価された翻訳後修飾の変化が、翻訳の変化を示す、請求項1から6のいずれか一項に記載の方法。
- 前記翻訳後修飾の構造の変化が、全体的な翻訳の減少を示す、請求項7に記載の方法。
- 前記モニタリングが、PDの進行をモニタリングすること、治療に対する反応をモニタリングすること、PDの寛解をモニタリングすること、またはPDの再発をモニタリングすることを含む、請求項1から8のいずれかに記載の方法。
- 前記診断が、前記対象をPDのサブグループに層別化することを含む、請求項1から9のいずれか一項に記載の方法。
- 前記試料が、皮膚生検試料、血液試料、細胞試料、組織試料、または体液である、請求項1から10のいずれかに記載の方法。
- 前記試料が、細胞試料である、請求項11に記載の方法。
- 前記細胞試料が、線維芽細胞および/または血液細胞である、請求項12に記載の方法。
- PDを診断、分類診断またはモニタリングするための、またはPD患者を層別化するためのキットであって、
SNX2及び/又はLIMA1の発現、ならびに
以下のグループ(1)~(3):
(1)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1LおよびRPL27、
(2)RASA1MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167AおよびASNS、ならびに
(3)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1L、RPL27、MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、RA-SA1、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167A、ASNS、FAM120A、ADAR、MAP1A、COL5A、BCL9L、USP7、RECK、CNOT7、NKIRAS1、ARPC5、CPN31、TMEM208、CRIP2、GDI1、USP9X、ADRM1、PEF1、YIF1B、GHITM、CANX、TNS1、OGDH、TNPO1、PEPD、HNRNFA3、MAP4、ALDH18A1、DDX21、DERL1、TPM2、NPM1、CLIC4、HLA-A、CDC41、STT3A、RHOA、CTNNB1、TRAM1、PLS3、SSR3、CTSK、NCBP1、PTRH2、SLC35B2、SF3B3、SLC2A14、SLC2A3、NUCB2、HEL-S-109、SEC61G、CLPTM1、PRMT1、ABCF2、VAMP7、RTCA、AEBP1、CPXM2、S100A16、RRAGD、RRAGC、EHD1、PALLD、CERS2、RPL17、RTN1、RAB8B、RPS15A、PYCR1、RAB5A、LOX、SEC61B、RPL36AL、PAWRおよびAPOL6から選択される遺伝子によりコードされる1種または複数のタンパク質
から選択される少なくとも1つを、
検出するための試薬を含む、キット。 - PDの診断の補助、分類診断の補助またはモニタリングするための、またはPD患者の層別化の補助をするためのキットの使用であって、前記キットが、
SNX2及び/又はLIMA1の発現、ならびに
以下のグループ(1)~(3):
(1)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1LおよびRPL27、
(2)RASA1MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167AおよびASNS、ならびに
(3)RRS1、TFRC、RASA1、NRAS、KRT36、Q56UQ5、PPIC、TRIM25、JAGN1、WDR36、CSE1L、RPL27、MX1、APOL2、DBI、ADA1B0GVG8、ERLEC1、TXNL1、TMSB10、CCDC50、BAG3、RA-SA1、CHMP4B、EIF2S2、HNRNPH1、NACA、GNL3、PSMC1、ACOX1、TMEM167A、ASNS、FAM120A、ADAR、MAP1A、COL5A、BCL9L、USP7、RECK、CNOT7、NKIRAS1、ARPC5、CPN31、TMEM208、CRIP2、GDI1、USP9X、ADRM1、PEF1、YIF1B、GHITM、CANX、TNS1、OGDH、TNPO1、PEPD、HNRNFA3、MAP4、ALDH18A1、DDX21、DERL1、TPM2、NPM1、CLIC4、HLA-A、CDC41、STT3A、RHOA、CTNNB1、TRAM1、PLS3、SSR3、CTSK、NCBP1、PTRH2、SLC35B2、SF3B3、SLC2A14、SLC2A3、NUCB2、HEL-S-109、SEC61G、CLPTM1、PRMT1、ABCF2、VAMP7、RTCA、AEBP1、CPXM2、S100A16、RRAGD、RRAGC、EHD1、PALLD、CERS2、RPL17、RTN1、RAB8B、RPS15A、PYCR1、RAB5A、LOX、SEC61B、RPL36AL、PAWRおよびAPOL6から選択される遺伝子によりコードされる1種または複数のタンパク質
から選択される少なくとも1つを、
検出するための試薬を含む、使用。
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PCT/FI2017/050892 WO2018109277A1 (en) | 2016-12-14 | 2017-12-14 | Diagnosis of parkinson's disease on the basis of decreased overall translation |
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WO2010005077A1 (ja) | 2008-07-11 | 2010-01-14 | 財団法人ヒューマンサイエンス振興財団 | パーキンソン病の疾患関連たんぱく質およびその使用 |
WO2013098786A1 (en) | 2011-12-30 | 2013-07-04 | Universita' Degli Studi Dell'insubria | Method for the in vitro diagnosis of parkinson's disease |
US20160244833A1 (en) | 2015-02-25 | 2016-08-25 | Rosalind Franklin University Of Medicine And Science | Methods and kits for diagnosing, prognosing and monitoring parkinson's disease |
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US20140141986A1 (en) * | 2011-02-22 | 2014-05-22 | David Spetzler | Circulating biomarkers |
WO2015157514A1 (en) | 2014-04-09 | 2015-10-15 | The Johns Hopkins University | Ribosomal protein s15 phosphorylation mediates lrrk2 neurodegeneration in parkinson's disease |
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WO2010005077A1 (ja) | 2008-07-11 | 2010-01-14 | 財団法人ヒューマンサイエンス振興財団 | パーキンソン病の疾患関連たんぱく質およびその使用 |
WO2013098786A1 (en) | 2011-12-30 | 2013-07-04 | Universita' Degli Studi Dell'insubria | Method for the in vitro diagnosis of parkinson's disease |
US20160244833A1 (en) | 2015-02-25 | 2016-08-25 | Rosalind Franklin University Of Medicine And Science | Methods and kits for diagnosing, prognosing and monitoring parkinson's disease |
Non-Patent Citations (3)
Title |
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IAN MARTIN,Decoding Parkinson's Disease Pathogenesis: The Role of Deregulated mRNA Translation,JOURNAL OF PARKINSON'S DISEASE,2016年,Vol. 6, No. 1, ,p17-27 |
TAYMANS JEAN-MARC ET AL,Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis,TRENDS IN MOLECULAR MEDICINE,2015年,Vol. 21, No. 8,p466-472 |
ZHANG TERRY ET AL,11.24 Determination of biomarker proteins for Parkinson's disease using differential quantitative proteomic analysis with clCAT and two-dimensional chromatography on a nanoelectrospray linear-lon trap LC/MS system, MOLECULAR & CELLULAR PROTEOMICS,2004年,Vol. 3, No. 10, Suppl. S144 |
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