341a3e90042d72f9aaf1e68c2a7235d9 pmc_10302771.pdf 66b5dc8cae79fe4ce3d1a7f9b01d1e13fc55fb91 pmc_10302771.pdf 6952c2817d38a460430d63b3089ea145734af272e95c0221354a171e31d3b96a pmc_10302771.pdf Title: New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics Subject: Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD. Keywords: animal models; constipation; dopamine; gastrointestinal; gut-brain axis; lipidome;microbiota; non-motor symptoms; Parkinson’s disease; probiotics Author: Lorena Ortega Moreno, Ana Bagues, Vicente Martínez and Raquel Abalo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jun 16 11:26:00 2023 CEST ModDate: Fri Jun 16 11:28:06 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 36 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1138075 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BYAHDB+VnURWPalladioL Type 1 Custom yes yes no 10 0 RZOWYX+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 IEKHGC+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 PIRRZD+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 GIHBLH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 75 0 GIHBLI+PalatinoLinotype CID TrueType Identity-H yes yes yes 78 0 GIHBLJ+PalatinoLinotype TrueType WinAnsi yes yes no 84 0 GIHBLL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 87 0 GIHCGI+PalatinoLinotype TrueType MacRoman yes yes no 90 0 XPNXUH+EURM10 Type 1 Builtin yes yes no 97 0 ANOPQK+CMSY10 Type 1 Builtin yes yes no 125 0 GIHGCG+Calibri,Bold CID TrueType Identity-H yes yes yes 152 0 GIHGCH+Calibri CID TrueType Identity-H yes yes yes 158 0 GIHGDI+Calibri,BoldItalic CID TrueType Identity-H yes yes yes 164 0 GIHBLH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 170 0 GIHBLI+PalatinoLinotype CID TrueType Identity-H yes yes yes 173 0 GIHBLJ+PalatinoLinotype TrueType WinAnsi yes yes no 179 0 GIHBLL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 182 0 GIHCGI+PalatinoLinotype TrueType MacRoman yes yes no 185 0 QGYAWM+SFRM0800 Type 1 Custom yes yes no 203 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-02-02 02:33:44 CET RepresentationInformation: pmc_10302771.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-01-17 02:26:35 CET Size: 1138075 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 1120 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Parkinson’s Disease: Pathogeny, Risk/Protection Factors, and Gut Involvement Destination: section.2 Item: Title: Gastrointestinal Motor Function in Animal Models of Parkinson’s Disease Destination: section.3 Children: Item: Title: Rodent-Based Animal Models of PD Destination: subsection.3.1 Children: Item: Title: Genetic Models Destination: subsubsection.3.1.1 Item: Title: Neurotoxin-Based Models Destination: subsubsection.3.1.2 Item: Title: Evaluation of GI Motor Function in PD Models Destination: subsection.3.2 Item: Title: Intestinal Microbiota and PD Destination: section.4 Children: Item: Title: Underlying Mechanisms Associating Intestinal Dysbiosis and PD Destination: subsection.4.1 Item: Title: Microbiota-Based Therapies for PD Destination: subsection.4.2 Item: Title: Lipidomics as a New Tool to Identify Biomarkers in Parkinson’s Disease Destination: section.5 Children: Item: Title: Lipidomics Approaches Destination: subsection.5.1 Item: Title: Lipids and Parkinson’s Disease Destination: subsection.5.2 Children: Item: Title: Fatty Acyls Destination: subsubsection.5.2.1 Item: Title: Glycerolipids, Glycerophospholipids, and Sphingolipids Destination: subsubsection.5.2.2 Item: Title: Sterols Destination: subsubsection.5.2.3 Item: Title: Lipidomics Analysis in Parkinson’s Disease Destination: subsection.5.3 Item: Title: Microbiota, Probiotics, and Lipidomics in Parkinson’s Disease Destination: subsection.5.4 Item: Title: Conclusions Destination: section.6 Item: Title: References Destination: section.7 Info: Title: New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics Author: Lorena Ortega Moreno, Ana Bagues, Vicente Martínez and Raquel Abalo Subject: Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD. 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