c877e592cd5b7ba7d90a95529800fbe6 intjoumolsci_a2009v10p724.pdf af51db1d3b82fd3f142312833edc8d9f197f689d intjoumolsci_a2009v10p724.pdf 348d652ae5168c25dce8f395f6df5ce026198f30028c365747617a152493d4a4 intjoumolsci_a2009v10p724.pdf Title: Molecular Pathology of Lewy Body Diseases Subject: Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pathways also involved in the pathology of synucleinopathies. Widespread mitochondrial dysfunction is very closely related to disease development. The impairment of protein degradation pathways, including both the ubiquitin-proteasome system and the autophagy-lysosome pathway also play an important role during the development of Lewy body diseases. Finally, differential expression changes of isoforms corresponding to genes primarily involved in Lewy body formation point to alternative splicing as another important mechanism in the development of Parkinson’s disease, as well as dementia with Lewy bodies. The present paper attempts to give an overview of recent molecular findings related to the pathogenesis of Lewy body diseases. Keywords: Lewy body diseases; Parkinson disease; dementia with Lewy bodies; alpha-synuclein; molecular chaperones; mitochondrial dysfunction; proteosomal dysfunction; alternative splicing; differential isoform expression Author: Katrin Beyer Creator: PScript5.dll Version 5.2.2 Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Wed Feb 25 15:09:35 2009 ModDate: Fri Mar 4 12:34:14 2016 Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.22 x 842 pts (A4) Page rot: 0 File size: 102176 bytes Optimized: yes PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TimesNewRomanPS-ItalicMT Type 1 WinAnsi no no no 96 0 TimesNewRomanPS-ItalicMT TrueType WinAnsi no no no 87 0 TimesNewRomanPS-BoldMT TrueType WinAnsi no no no 88 0 TimesNewRomanPSMT TrueType WinAnsi no no no 89 0 TimesNewRomanPS-BoldItalicMT TrueType WinAnsi no no no 71 0 FLKGDE+SymbolMT CID TrueType Identity-H yes yes yes 72 0 ArialMT TrueType WinAnsi no no no 73 0 Verdana TrueType WinAnsi no no no 74 0 Jhove (Rel. 1.6, 2011-01-04) Date: 2016-03-11 04:07:51 CET RepresentationInformation: intjoumolsci_a2009v10p724.pdf ReportingModule: PDF-hul, Rel. 1.8 (2009-05-22) LastModified: 2016-03-04 12:34:18 CET Size: 102176 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 100 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: OneColumn PageMode: UseThumbs Info: Title: Molecular Pathology of Lewy Body Diseases Author: Katrin Beyer Subject: Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pathways also involved in the pathology of synucleinopathies. Widespread mitochondrial dysfunction is very closely related to disease development. The impairment of protein degradation pathways, including both the ubiquitin-proteasome system and the autophagy-lysosome pathway also play an important role during the development of Lewy body diseases. Finally, differential expression changes of isoforms corresponding to genes primarily involved in Lewy body formation point to alternative splicing as another important mechanism in the development of Parkinson’s disease, as well as dementia with Lewy bodies. The present paper attempts to give an overview of recent molecular findings related to the pathogenesis of Lewy body diseases. Keywords: Lewy body diseases; Parkinson disease; dementia with Lewy bodies; alpha-synuclein; molecular chaperones; mitochondrial dysfunction; proteosomal dysfunction; alternative splicing; differential isoform expression Creator: PScript5.dll Version 5.2.2 Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Wed Feb 25 08:09:35 CET 2009 ModDate: Fri Mar 04 12:34:14 CET 2016 ID: 0x1cb09ff754aec2f02bca7d3153d77bb7, 0x13efa654b9364547814aa817c3d430d0 Filters: FilterPipeline: FlateDecode Fonts: Type0: Font: BaseFont: FLKGDE+SymbolMT Encoding: Identity-H ToUnicode: true Type1: Font: BaseFont: TimesNewRomanPS-ItalicMT FirstChar: 0 LastChar: 255 FontDescriptor: FontName: TimesNewRomanPS-ItalicMT Flags: Serif, Nonsymbolic, Italic FontBBox: -191, -250, 1031, 868 Encoding: WinAnsiEncoding TrueType: Font: BaseFont: TimesNewRomanPS-ItalicMT FirstChar: 32 LastChar: 146 FontDescriptor: FontName: TimesNewRomanPS-ItalicMT Flags: Serif, Nonsymbolic, Italic FontBBox: -498, -307, 1120, 1023 Encoding: WinAnsiEncoding Font: BaseFont: TimesNewRomanPS-BoldItalicMT FirstChar: 32 LastChar: 32 FontDescriptor: FontName: TimesNewRomanPS-BoldItalicMT Flags: Serif, Nonsymbolic, Italic FontBBox: -547, -307, 1206, 1032 Encoding: WinAnsiEncoding Font: BaseFont: TimesNewRomanPSMT FirstChar: 32 LastChar: 252 FontDescriptor: FontName: TimesNewRomanPSMT Flags: Serif, Nonsymbolic FontBBox: -568, -307, 2000, 1007 Encoding: WinAnsiEncoding Font: BaseFont: ArialMT FirstChar: 32 LastChar: 32 FontDescriptor: FontName: ArialMT Flags: Nonsymbolic FontBBox: -665, -325, 2000, 1006 Encoding: WinAnsiEncoding Font: BaseFont: TimesNewRomanPS-BoldMT FirstChar: 32 LastChar: 224 FontDescriptor: FontName: TimesNewRomanPS-BoldMT Flags: Serif, Nonsymbolic FontBBox: -558, -307, 2000, 1026 Encoding: WinAnsiEncoding Font: BaseFont: Verdana FirstChar: 46 LastChar: 46 FontDescriptor: FontName: Verdana Flags: Nonsymbolic FontBBox: -50, -207, 1447, 1000 Encoding: WinAnsiEncoding CIDFontType2: Font: BaseFont: FLKGDE+SymbolMT CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: FLKGDE+SymbolMT Flags: Symbolic FontBBox: 0, -220, 1113, 1005 FontFile2: true XMP: 2009-02-25T15:09:35+08:00 PScript5.dll Version 5.2.2 2016-03-04T12:34:14+01:00 2016-03-04T12:34:14+01:00 Acrobat Distiller 8.1.0 (Windows) Lewy body diseases; Parkinson disease; dementia with Lewy bodies; alpha-synuclein; molecular chaperones; mitochondrial dysfunction; proteosomal dysfunction; alternative splicing; differential isoform expression application/pdf Katrin Beyer Montserrat Domingo-Sàbat Aurelio Ariza Molecular Pathology of Lewy Body Diseases Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pathways also involved in the pathology of synucleinopathies. Widespread mitochondrial dysfunction is very closely related to disease development. The impairment of protein degradation pathways, including both the ubiquitin-proteasome system and the autophagy-lysosome pathway also play an important role during the development of Lewy body diseases. Finally, differential expression changes of isoforms corresponding to genes primarily involved in Lewy body formation point to alternative splicing as another important mechanism in the development of Parkinson’s disease, as well as dementia with Lewy bodies. The present paper attempts to give an overview of recent molecular findings related to the pathogenesis of Lewy body diseases. 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