SLC Solute Carrier Transporters and Neurodegenerative Disorders: Drawing Attention to Cationic Amino Acid Transporters 1 and 2

Bernstein, Hans‐Gert; Keilhoff, Gerburg; Dobrowolny, Henrik; Steiner, Johann

doi:10.9758/cpn.2020.18.3.467

Cited by 3 publications

References 12 publications

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Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Toward discovering a novel family of peptides targeting neuroinflammatory states of brain microglia and astrocytes

Koss

Son

et al. 2023

Journal of Neurochemistry

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Microglia are immune‐derived cells critical to the development and healthy function of the brain and spinal cord, yet are implicated in the active pathology of many neuropsychiatric disorders. A range of functional phenotypes associated with the healthy brain or disease states has been suggested from in vivo work and were modeled in vitro as surveying, reactive, and primed sub‐types of primary rat microglia and mixed microglia/astrocytes. It was hypothesized that the biomolecular profile of these cells undergoes a phenotypical change as well, and these functional phenotypes were explored for potential novel peptide binders using a custom 7 amino acid‐presenting M13 phage library (SX7) to identify unique peptides that bind differentially to these respective cell types. Surveying glia were untreated, reactive were induced with a lipopolysaccharide treatment, recovery was modeled with a potent anti‐inflammatory treatment dexamethasone, and priming was determined by subsequently challenging the cells with interferon gamma. Microglial function was profiled by determining the secretion of cytokines and nitric oxide, and expression of inducible nitric oxide synthase. After incubation with the SX7 phage library, populations of SX7‐positive microglia and/or astrocytes were collected using fluorescence‐activated cell sorting, SX7 phage was amplified in Escherichia coli culture, and phage DNA was sequenced via next‐generation sequencing. Binding validation was done with synthesized peptides via in‐cell westerns. Fifty‐eight unique peptides were discovered, and their potential functions were assessed using a basic local alignment search tool. Peptides potentially originated from proteins ranging in function from a variety of supportive glial roles, including synapse support and pruning, to inflammatory incitement including cytokine and interleukin activation, and potential regulation in neurodegenerative and neuropsychiatric disorders.image

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Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines

Pochini

2024

Front. Mol. Biosci.

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Polyamines interact with different molecular targets to regulate a vast range of cellular processes. A network of enzymes and transport systems is crucial for the maintenance of polyamine homeostasis. Indeed, polyamines after synthesis must be distributed to the various tissues and some intracellular organelles. Differently from the well characterized enzymes devoted to polyamine synthesis, the transport systems are not unequivocally identified or characterized. Besides some ATPases which have been identified as polyamine transporters, much less is known about solute carriers (SLC) involved in the transport of these compounds. Only two SLCs have been unequivocally identified as polyamine transporters: SLC18B1 (VPAT) and SLC22A4 (OCTN1). Transport studies have been performed with cells transfected with the cDNAs encoding the two and other SLCs or, in the case of OCTN1, also by in vitro assay using proteoliposomes harboring the recombinant human protein. According to the role proposed for OCTN1, polyamines have been associated with prolonged and quality of life. This review provides an update on the most recent findings concerning the polyamine transporters or the prediction of the putative ones.

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SLC Solute Carrier Transporters and Neurodegenerative Disorders: Drawing Attention to Cationic Amino Acid Transporters 1 and 2

Cited by 3 publications

References 12 publications

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Toward discovering a novel family of peptides targeting neuroinflammatory states of brain microglia and astrocytes

Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines

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