cdabcf9ef817390692f393593f687fbd pmc_10049671.pdf 259c85ec9d32931edfe269e4a65182a5237e8ce3 pmc_10049671.pdf ea7650e0186230d96b4ae861225c3d7b15a2eef1a9ba42f8e3460931590200e2 pmc_10049671.pdf Title: Fabry Disease and Central Nervous System Involvement: From Big to Small, from Brain to Synapse Subject: Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) secondary to mutations in the GLA gene that causes dysfunctional activity of lysosomal hydrolase -galactosidase A and results in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). The endothelial accumulation of these substrates results in injury to multiple organs, mainly the kidney, heart, brain and peripheral nervous system. The literature on FD and central nervous system involvement is scarce when focusing on alterations beyond cerebrovascular disease and is nearly absent in regard to synaptic dysfunction. In spite of that, reports have provided evidence for the CNS’ clinical implications in FD, including Parkinson’s disease, neuropsychiatric disorders and executive dysfunction. We aim to review these topics based on the current available scientific literature. Keywords: Fabry disease; synapse; neurotransmitter; neurotransmission; lysosome; metabolism Author: Elisenda Cortés-Saladelafont, Julián Fernández-Martín and Saida Ortolano Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 9 09:49:12 2023 CET ModDate: Fri Mar 10 11:15:05 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 881085 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 VJAUGW+VnURWPalladioL Type 1 Custom yes yes no 15 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 19 0 LBZHMV+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 OTQZDF+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 RMOPKY+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi 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Related to CNS Involvement in FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: The Pain in Fabry Disease Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Parkinson’s Disease (PD) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Neurodegeneration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Psychiatric Manifestations and Cognitive Functioning Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: MRI Abnormalities (Other Than Cerebrovascular Disease) in FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Reduced Intracranial Volume and Thalamic and Hippocampal Atrophy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Motor Cortex and Cerebellar and Nigrostriatal Pathway Involvement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Neurodegeneration, Neuronal Dysfunction and Hypometabolic Brain Regions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: MRI Changes in Children and Adolescents with FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Neuropathology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Animal Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Mouse and Rat Models and the Recapitulation of FD Phenotype Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Alterations in the Autophagy Lysosome Pathway (ALP) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: PD and Brain Protein Aggregation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Gene Expression Related to Neuronal and Synaptic Dysfunction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: New Treatment Options with Impact on the CNS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Induced Pluripotent Stem Cell Models in FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Energy Metabolism and Neurotransmission in FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Energy Metabolism and Neurotransmission in the CNS, Lysosomal Disorders and Glycosphingolipodoses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Mitochondrial Involvement, Impaired Autophagic Function and Altered Neurotransmitter Release in FD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Different Neurotransmitter Systems Altered in FD, and Their Possible Role in Clinical Manifestations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Children: Item: Title: Acetylcholine (ACh) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Dopamine (DA) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Dopamine and Acetylcholine Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Serotonin (5-HT) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Info: Title: Fabry Disease and Central Nervous System Involvement: From Big to Small, from Brain to Synapse Author: Elisenda Cortés-Saladelafont, Julián Fernández-Martín and Saida Ortolano Subject: Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) secondary to mutations in the GLA gene that causes dysfunctional activity of lysosomal hydrolase -galactosidase A and results in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). The endothelial accumulation of these substrates results in injury to multiple organs, mainly the kidney, heart, brain and peripheral nervous system. The literature on FD and central nervous system involvement is scarce when focusing on alterations beyond cerebrovascular disease and is nearly absent in regard to synaptic dysfunction. In spite of that, reports have provided evidence for the CNS’ clinical implications in FD, including Parkinson’s disease, neuropsychiatric disorders and executive dysfunction. We aim to review these topics based on the current available scientific literature. 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