08ef2c6901ff4a6ae56671ce6fc7680c pmc_19399218.pdf 90db08203b6f4ed6b63ee985ebe873e86bc9de00 pmc_19399218.pdf 157a88911ab4027f7b266100d77645fa770bf91d69ba53e497ea0d20478d19a7 pmc_19399218.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 08:09:35 2009 CET ModDate: Thu Feb 26 09:54:25 2009 CET Custom Metadata: no Metadata Stream: yes 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: 117926 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- 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-ItalicMT Type 1 WinAnsi no no no 100 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. 1.28.0, 2023-05-18) Date: 2024-05-07 05:48:33 CEST RepresentationInformation: pmc_19399218.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2020-08-10 04:05:54 CEST Size: 117926 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 105 FreeObjects: 1 IncrementalUpdates: 4 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: Thu Feb 26 09:54:25 CET 2009 ID: 0x1cb09ff754aec2f02bca7d3153d77bb7, 0xb2dc93e4018ada4da7983d0b76607bfb 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: TimesNewRomanPS-BoldMT FirstChar: 32 LastChar: 224 FontDescriptor: FontName: TimesNewRomanPS-BoldMT Flags: Serif, Nonsymbolic FontBBox: -558, -307, 2000, 1026 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: 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 2009-02-26T09:54:25+01:00 2009-02-26T09:54:25+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. Lewy body diseases Parkinson disease dementia with Lewy bodies alpha-synuclein molecular chaperones mitochondrial dysfunction proteosomal dysfunction alternative splicing differential isoform expression uuid:af707512-0053-4297-a8db-dc66e284b2ff uuid:a4cab9e5-dcd5-4313-aef9-94c27135da1d False Pages: Page: Label: 1 Page: Label: 2 Page: Label: 3 Page: Label: 4 Page: Label: 5 Page: Label: 6 Page: Label: 7 Page: Label: 8 Page: Label: 9 Page: Label: 10 Page: Label: 11 Page: Label: 12 Page: Label: 13 Page: Label: 14 Page: Label: 15 Page: Label: 16 Page: Label: 17 Page: Label: 18 Page: Label: 19 Page: Label: 20 Page: Label: 21 Page: Label: 22 Checksum: 3ecaf22e Type: CRC32 Checksum: 08ef2c6901ff4a6ae56671ce6fc7680c Type: MD5 Checksum: 90db08203b6f4ed6b63ee985ebe873e86bc9de00 Type: SHA-1 Checksum: 157a88911ab4027f7b266100d77645fa770bf91d69ba53e497ea0d20478d19a7 Type: SHA-256