A strong association between VEGF-A rs28357093 and amyotrophic lateral sclerosis: a brazilian genetic study

Costa, Caroline Christine Pincela da; Lima, Nayane Soares de; Bento, Dhiogo da Cruz Pereira; Santos, Rodrigo da Silva; Reis, Ângela Adamski da Silva

doi:10.1007/s11033-022-07647-z

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…PNPLA3 [174], ACTN2 [175], MMP15 [176], SVEP1 [177], CPB2 [178], DYSF (dysferlin) [179], ADAMTSL2 [180], NINJ2 [181], LRP2 [106], PHLDA3 [182], LIPC (lipase C, hepatic type) [183], CARNS1 [184], PRODH (proline dehydrogenase 1) [185], TRPV6 [186], CNDP1 [187], DHCR7 [188], KCNE5 [189] SAA1 [190], ADSS1 [191], ACADS (acyl-CoA dehydrogenase short chain) [192], ADAP1 [193], KLK10 [194], HCN2 [195], F11 [196], RNASE1 [197], GNLY (granulysin) [198], EVA1A [199], CIRBP (cold inducible RNA binding protein) [200], EDIL3 [201], NOXA1 [202], ANGPTL2 [203], CYP2A6 [204] and CTNNA3 [205] might be associated with cardiovascular diseases progression. The abnormal expression of CCL18 [206], EOMES (eomesodermin) [207], GZMA (granzyme A) [208], HLA-DRB5 [209], GPNMB (glycoprotein nmb) [210], PRPH (peripherin) [211], HGF (hepatocyte growth factor) [212], TTR (transthyretin) [213], VEGFA (vascular endothelial growth factor A) [214], CHI3L1 [215], AATK (apoptosis associated tyrosine kinase) [216], SREBF1 [217], OLIG2 [218], ATF3 [219], NGFR (nerve growth factor receptor) [220], ADAMTS4 [221], LMNA (lamin A/C) [222], MT3 [223], DAO (D-amino acid oxidase) [224], AATK (apoptosis associated tyrosine kinase) [216] and LGALS3BP [225] might be related to the progression of amyotrophic lateral sclerosis. SLAMF7 [226], GPR174 [227], FCRL3 [228], SLAMF6 [229], EOMES (eomesodermin) [230], CCR4 [231], CCR2 [232], CD48 [233], CD3E [234], CCL26 [235], CCL4 [236], SLAMF1 [237], CD24 [238], IKZF3 [239], CD2 […”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Multiple sclerosis (MS) is the main reason for disability caused by autoimmunity. However, effective biomarkers for MS have not been identified. This study explored the molecular mechanisms and potential therapeutic targets for MS occurrence and progression using bioinformatics and next generation sequencing (NGS) data analysis. NGS data GSE138614, including patients with MS and 25 normal control samples, were obtained from Gene Expression Omnibus (GEO) database Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. Protein–protein interaction (PPI) network and module analyses were performed based on the DEGs. MiRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were built by Cytoscape to predict the underlying microRNAs (miRNAs) and transcription factors (TFs) associated with hub genes. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. A total of 959 DEGs (479 up regulated genes and 480 down regulated genes) were detected. The GO terms and pathways of DEGs involve immune system process, developmental process, immune system and regulation of cholesterol biosynthesis by SREBP (SREBF). The network analysis revealed that hub genes include LCK, PYHIN1, SLAMF1, DOK2, TAB2, CFTR, RHOB, LMNA, EGLN3 and ERBB3 might be involved in the development of MS. The present investigation illustrates a characteristic gene profile in MS, which might contribute to the interpretation of the progression of MS and provide novel biomarkers and therapeutic targets for MS.

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Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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“…ALS patients frequently harbor mutations in the vascular endothelial growth factor (VEGF) gene; (motor cortical) protein expression and VEGF serum levels are reduced in ALS rodent models and patients [ 58 , 59 , 60 ]. VEGF exerts trophic and neuroprotective effects on motor neurons [ 61 ].…”

Section: Vascular Supply Mediates Brain Vascular Healthmentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

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Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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“…ACA, anterior cerebral artery; ALS, amyotrophic lateral sclerosis; BBB, blood-brain barrier; BM, basement membrane; CBF, cerebral blood flow; CNS, central nervous system; COL6A1, collagen VI alpha1; CVR, cerebrovascular reserve; EC, endothelial cell; IgG, immunoglobulin G; IL, interleukin; MCA, middle cerebral artery; MRI, magnetic resonance imaging; NVU, neurovascular unit; pTDP43, phosphorylated aggregates of 43 kDa transactive response DNA-binding protein; PVS, perivascular space; RBC, red blood cell; ROS, reactive oxygen species; SASP, senescence-associated secretory phenotype; SPP1, secreted phosphoprotein 1; VEGF, vascular endothelial growth factor. ALS patients frequently harbor mutations in the vascular endothelial growth factor (VEGF) gene; protein expression and VEGF serum levels are reduced in ALS rodent models and patients [58][59][60]. VEGF exerts trophic and neuroprotective effects on motor neurons [61].…”

Section: Vascular Supply -Molecular and Cellular Underpinnings In Alsmentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber¹,

Bernal²,

Ulbrich³

et al. 2023

Preprint

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Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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A strong association between VEGF-A rs28357093 and amyotrophic lateral sclerosis: a brazilian genetic study

Cited by 5 publications

References 25 publications

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

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