scholarly journals A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System

2021 ◽  
Vol 9 ◽  
Author(s):  
Patricia Pascual-Vargas ◽  
Patricia C. Salinas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synapse Formation ◽  
Neuronal Circuits ◽  
Motor Tasks ◽  
Neuronal Connectivity ◽  
Post Translational Modifications ◽  
The Central Nervous System ◽  
And Function

The Wnt pathway is a key signalling cascade that regulates the formation and function of neuronal circuits. The main receptors for Wnts are Frizzled (Fzd) that mediate diverse functions such as neurogenesis, axon guidance, dendritogenesis, synapse formation, and synaptic plasticity. These processes are crucial for the assembly of functional neuronal circuits required for diverse functions ranging from sensory and motor tasks to cognitive performance. Indeed, aberrant Wnt–Fzd signalling has been associated with synaptic defects during development and in neurodegenerative conditions such as Alzheimer’s disease. New studies suggest that the localisation and stability of Fzd receptors play a crucial role in determining Wnt function. Post-translational modifications (PTMs) of Fzd are emerging as an important mechanism that regulates these Wnt receptors. However, only phosphorylation and glycosylation have been described to modulate Fzd function in the central nervous system (CNS). In this review, we discuss the function of Fzd in neuronal circuit connectivity and how PTMs contribute to their function. We also discuss other PTMs, not yet described in the CNS, and how they might modulate the function of Fzd in neuronal connectivity. PTMs could modulate Fzd function by affecting Fzd localisation and stability at the plasma membrane resulting in local effects of Wnt signalling, a feature particularly important in polarised cells such as neurons. Our review highlights the importance of further studies into the role of PTMs on Fzd receptors in the context of neuronal connectivity.

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

scholarly journals miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142098118
Author(s):  
Alexander D. Walsh ◽  
Linda T. Nguyen ◽  
Michele D. Binder
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Approaches ◽  
Ribonucleic Acids ◽  
Microglial Phagocytosis ◽  
The Central Nervous System ◽  
And Function ◽  
Ms Pathogenesis

Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.

scholarly journals The Role of Neurod Genes in Brain Development, Function, and Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Svetlana Tutukova ◽  
Victor Tarabykin ◽  
Luis R. Hernandez-Miranda
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Postnatal Life ◽  
Neural Lineage ◽  
Helix Loop Helix ◽  
The Central Nervous System ◽  
Bhlh Factors ◽  
And Function

Transcriptional regulation is essential for the correct functioning of cells during development and in postnatal life. The basic Helix-loop-Helix (bHLH) superfamily of transcription factors is well conserved throughout evolution and plays critical roles in tissue development and tissue maintenance. A subgroup of this family, called neural lineage bHLH factors, is critical in the development and function of the central nervous system. In this review, we will focus on the function of one subgroup of neural lineage bHLH factors, the Neurod family. The Neurod family has four members: Neurod1, Neurod2, Neurod4, and Neurod6. Available evidence shows that these four factors are key during the development of the cerebral cortex but also in other regions of the central nervous system, such as the cerebellum, the brainstem, and the spinal cord. We will also discuss recent reports that link the dysfunction of these transcription factors to neurological disorders in humans.

scholarly journals l-Serine in disease and development

2003 ◽  
Vol 371 (3) ◽  
pp. 653-661 ◽  
Author(s):  
Tom J. de KONING ◽  
Keith SNELL ◽  
Marinus DURAN ◽  
Ruud BERGER ◽  
Bwee-Tien POLL-THE ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Cellular Proliferation ◽  
De Novo ◽  
Essential Amino Acids ◽  
Purine Nucleotides ◽  
The Central Nervous System ◽  
And Function

The amino acid l-serine, one of the so-called non-essential amino acids, plays a central role in cellular proliferation. l-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, l-serine is a conditional essential amino acid, because it cannot be synthesized in sufficient quantities to meet the cellular demands for its utilization. In recent years, l-serine and the products of its metabolism have been recognized not only to be essential for cell proliferation, but also to be necessary for specific functions in the central nervous system. The findings of altered levels of serine and glycine in patients with psychiatric disorders and the severe neurological abnormalities in patients with defects of l-serine synthesis underscore the importance of l-serine in brain development and function. This paper reviews these recent insights into the role of l-serine and the pathways of l-serine utilization in disease and during development, in particular of the central nervous system.

Role of a nurse in the rehabilitation of children using ReviMotion hardware and software complex

2020 ◽  
pp. 49-56
Author(s):  
T. Shirshova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
School Age Children ◽  
Equipment Management ◽  
School Age ◽  
Rehabilitation Process ◽  
Software Complex ◽  
Trained Personnel ◽  
The Central Nervous System

Disorders of the musculoskeletal system in school-age children occupy 1-2 places in the structure of functional abnormalities. Cognitive impairment without organic damage to the central nervous system is detected in 30-56% of healthy school children. Along with the increase in the incidence rate, the demand for rehabilitation systems, which allow patients to return to normal life as soon as possible and maintain the motivation for the rehabilitation process, is also growing. Adaptation of rehabilitation techniques, ease of equipment management, availability of specially trained personnel and availability of technical support for complexes becomes important.

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