Diseases of the Synaptic Vesicle: A Potential New Group of Neurometabolic Disorders Affecting Neurotransmission

Cortès‐Saladelafont, Elisenda; Tristán-Noguero, Alba; Artuch, Rafael; Altafaj, Xavier; Bayés, Àlex; García‐Cazorla, Àngels

doi:10.1016/j.spen.2016.11.005

Cited by 25 publications

(25 citation statements)

References 43 publications

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“…69 Mutations coding for many different proteins that regulate the SV exocytic-endocytic pathway have been described as responsible of a variety of disorders that share general characteristics of complex molecule disorders. 70,71 In particular, trafficking, intracellular vesiculation, chaperon proteins (folding, unfolding and disaggregation), protein-protein, protein-lipid, and lipid-lipid interaction compose the main mechanisms of this group of diseases. 71 Aminoacyl tRNA synthetases deficiencies compose a group of already more than 30 disorders With the exception of GARS and KARS, mitochondrial and cytoplasmic aaRSs are encoded by distinct nuclear genes.…”

Section: Cellular Trafficking and Processing Disordersmentioning

confidence: 99%

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians

Saudubray

Mochel

Lamari

et al. 2019

J of Inher Metab Disea

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In view of the rapidly expanding number of IMD discovered by next generation sequencing, we propose a simplified classification of IMD that mixes elements from a clinical diagnostic perspective and a pathophysiological approach based on three large categories. We highlight the increasing importance of complex molecule metabolism and its connection with cell biology processes. Small molecule disorders have biomarkers and are divided in two subcategories: accumulation and deficiency. Accumulation of small molecules leads to acute or progressive postnatal “intoxication”, present after a symptom‐free interval, aggravated by catabolism and food intake. These treatable disorders must not be missed! Deficiency of small molecules is due to impaired synthesis of compounds distal to a block or altered transport of essential molecules. This subgroup shares many clinical characteristics with complex molecule disorders. Complex molecules (like glycogen, sphingolipids, phospholipids, glycosaminoglycans, glycolipids) are poorly diffusible. Accumulation of complex molecules leads to postnatal progressive storage like in glycogen and lysosomal storage disorders. Many are treatable. Deficiency of complex molecules is related to the synthesis and recycling of these molecules, which take place in organelles. They may interfere with fœtal development. Most present as neurodevelopmental or neurodegenerative disorders unrelated to food intake. Peroxisomal disorders, CDG defects of intracellular trafficking and processing, recycling of synaptic vesicles, and tRNA synthetases also belong to this category. Only few have biomarkers and are treatable. Disorders involving primarily energy metabolism encompass defects of membrane carriers of energetic molecules as well as cytoplasmic and mitochondrial metabolic defects. This oversimplified classification is connected to the most recent available nosology of IMD.

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Section: Cellular Trafficking and Processing Disordersmentioning

confidence: 99%

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians

Saudubray

Mochel

Lamari

et al. 2019

J of Inher Metab Disea

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“…The abnormal expression of signaling pathway can cause encephalitis and other neuronal dysfunctions. The changes in the synaptic vesicle, especially the synaptic vesicle cycle, can cause abnormal neurotransmitter activity ( Cortes-Saladelafont et al, 2016 ). For the ErbB signaling pathway, there were significant changes in the gene expression of ErbB signaling pathway in the brain tissues of the patients with HIV-associated dementia ( Shityakov, Dandekar & Forster, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the involvement of LncRNA in HIV-associated encephalitis using bioinformatics

Bao

Yin

et al. 2018

PeerJ

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BackgroundHIV-associated encephalitis (HIVE) is one of the common complications of HIV infection, and the pathogenesis of HIVE remains unclear, while lncRNA might be involved it. In this study, we made re-annotation on the expression profiling from the HIVE study in the public database, identified the lncRNA that might be involved in HIVE, and explored the possible mechanism.MethodsIn the GEO public database, the microarray expression profile () of three regions of brain tissues (white matter, frontal cortex and basal ganglia brain tissues) was chosen, updated annotation was performed to construct the non-cording-RNA (ncRNA) microarray data. Morpheus was used to identify the differential expressed ncRNA, and Genbank of NCBI was used to identify lncRNAs. The StarBase, PITA and miRDB databases were used to predict the target miRNAs of lncRNA. The TargetScan, PicTar and MiRanda databases were used to predict the target genes of miRNAs. The GO and KEGG pathway analysis were used to make function analysis on the targets genes.ResultsSeventeen differentially expressed lncRNAs were observed in the white matter of brain tissues, for which 352 target miRNAs and 6,659 target genes were predicted. The GO function analysis indicated that the lncRNAs were mainly involved in the nuclear transcription and translation processes. The KEGG pathway analysis showed that the target genes were significantly enriched in 33 signal pathways, of which 11 were clearly related to the nervous system function.DiscussionThe brand-new and different microarray results can be obtained through the updated annotation of the chips, and it is feasible to identify lncRNAs from ordinary chips. The results suggest that lncRNA may be involved in the occurrence and development of HIVE, which provides a new direction for further research on the diagnosis and treatment of HIVE.

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“…Defects of the synaptic vesicle and SV-related are a large group of disorders under characterization. These diseases affect the machinery involved in synaptic vesicle biogenesis (of vesicle-precursors in the neuronal soma); their transport along the axon and up to the pre-synaptic terminal, where SVs undergo exocytosis-endocytosis cycles (Cortès-Saladelafont et al 2016) will be discussed in detail in this same issue (Cortès-Saladelafont et al, this issue). Because this is an organelle-based category description, some of the diseases included as SV-related disorders overlap with other defects described in this article (classified by concrete neurobiological functions).…”

Section: Disorders Of the Synaptic Vesicle (And Sv-related)mentioning

confidence: 99%

Synaptic metabolism: a new approach to inborn errors of neurotransmission

Tristán-Noguero¹,

García‐Cazorla²

2018

J of Inher Metab Disea

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To date, inborn errors of neurotransmitters have been defined based on the classic concept of inborn error of metabolism (IEM), and they include defects in synthesis, catabolism, and transport pathways. However, the omics era is bringing insights into new diseases and is leading to an extended definition of IEM including new categories and mechanisms. Neurotransmission takes place at the synapse, the most specialized tight junction in the brain. The concept of "synaptic metabolism" would point to the specific chemical composition and metabolic functions of the synapse. Based on these specialized functions, we aim to provide a tentative overview about the major categories of IEM susceptible to affect neurotransmission. Small molecule defects (biogenic amines and amino acids) and energy defects are amongst the most prevalent diseases reported to disturb the concentration of CSF neurotransmitters. In these IEM, the neurological phenotypes have been largely described. Disorders of complex molecules are not typically considered as diseases affecting neurotransmission. However, most of them have been recently discovered and are involved in intracellular vesiculation, trafficking, processing, and quality control mechanisms. In this large group, neurotransmission is affected in disorders of chaperones and autophagy, disorders of the synaptic vesicle, and diseases affecting pre-synaptic membranes (synthesis and remodeling of complex lipids, defects of glycosylation). Disorders of the vesicle pools, receptor trafficking, and the chronobiology of neurotransmission are potentially emerging new categories. Finally, although not considered as IEM, channelopathies are a large group of diseases disturbing neurotransmitter homeostasis. New CSF biomarkers will probably contribute to improve the diagnosis of these disorders and find new therapeutic targets.

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Diseases of the Synaptic Vesicle: A Potential New Group of Neurometabolic Disorders Affecting Neurotransmission

Cited by 25 publications

References 43 publications

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians

Exploration of the involvement of LncRNA in HIV-associated encephalitis using bioinformatics

Synaptic metabolism: a new approach to inborn errors of neurotransmission

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