1,721,024 research outputs found
The synapsins: key actors of synapse function and plasticity
No full textThe synapsins are a family of neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms. Their best-characterised function is to modulate neurotransmitter release at the presynaptic terminal, by reversibly tethering synaptic vesicles (SVs) to the actin cytoskeleton. However, many recent data have suggested novel functions for synapsins in other aspects of the presynaptic physiology, such as SV docking, fusion and recycling. Synapsin activity is tightly regulated by several protein kinases and phosphatases, which modulate the association of synapsins to SVs as well as their interaction with actin filaments and other synaptic proteins. In this context, synapsins act as a link between extracellular stimuli and the intracellular signalling events activated upon neuronal stimulation. Genetic manipulation of synapsins in various in vivo models has revealed that, although not essential for the basic development and functioning of neuronal networks, these proteins are extremely important in the fine-tuning of neuronal plasticity, as shown by the epileptic phenotype and behavioural abnormalities characterising mouse lines lacking one or more synapsin isoforms.
In this review, we summarise the current knowledge about how the various members of the synapsin family are involved in the modulation of the presynaptic physiology. We give a comprehensive description of the molecular basis of synapsin function, as well as an overview of the more recent evidence linking mutations in the synapsin proteins to the onset of severe central nervous system diseases such as epilepsy and schizophrenia
Specificity Protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5’-Cytosine-Phosphoguanine (CpG) methylation
No full textThe development and function of the nervous system are directly dependent on a well defined pattern of gene expression. Indeed, perturbation of transcriptional activity or epigenetic modifications of chromatin can dramatically influence neuronal phenotypes. The phosphoprotein synapsin I (Syn I) plays a crucial role during axonogenesis and synaptogenesis as well as in synaptic transmission and plasticity of mature neurons. Abnormalities in SYN1 gene expression have been linked to important neuropsychiatric disorders, such as epilepsy and autism. SYN1 gene transcription is suppressed in non-neural tissues by the RE1-silencing transcription factor (REST); however, the molecular mechanisms that allow the constitutive expression of this genetic region in neurons have not been clarified yet. Herein we demonstrate that a conserved region of human and mouse SYN1 promoters contains cis-sites for the transcriptional activator Sp1 in close proximity to REST binding motifs. Through a series of functional assays, we demonstrate a physical interaction of Sp1 on the SYN1 promoter and show that REST directly inhibits Sp1-mediated transcription, resulting in SYN1 down-regulation. Upon differentiation of neuroblastoma Neuro2a cells, we observe a decrease in endogenous REST and a higher stability of Sp1 on target GC boxes, resulting in an increase of SYN1 transcription. Moreover, methylation of Sp1 cis-sites in the SYN1 promoter region could provide an additional level of transcriptional regulation. Our results introduce Sp1 as a fundamental activator of basal SYN1 gene expression, whose activity is modulated by the neural master regulator REST and CpG methylation
Interactions Between 2D Graphene-Based Materials and the Nervous Tissue
No full textIn recent years, the scientific community has witnessed an exponential increase in the use of graphene for biomedical applications. For what concerns neuroscience, the interest raised by this material is given by the fact that graphene nanosheets can be used as carriers for biomolecule delivery to the central nervous system. In this case, an important aspect is the evaluation of their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. Furthermore, graphene can be exploited as a substrate for tissue engineering. In this application, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation.
This chapter discusses the engineering of graphene nanosheets able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. Moreover, the use of graphene to develop three-dimensional scaffolds, or as a component of hybrid composites/multi-layer organic electronics devices, is described. The need of an accurate theoretical modeling of the interface between graphene and biological material is also addressed, by describing the interaction of graphene with proteins and cell membranes at the nanoscale
Corrigendum to "The synapsins: Key actors of synapse function and plasticity" [Prog. Neurobiol. 91 (4) (2010) 313-348]
No full textExpression of plasma membrane (PMCA) and sarco/endoplasmic reticulum (SERCA) Ca2+-ATPase pumps in cellular model of Huntington disease
No full textInteractions Between 2D Graphene-Based Materials and the Nervous Tissue
No full textIn recent years, the scientific community has witnessed an exponential increase in the use of graphene for biomedical applications. For what concerns neuroscience, the interest raised by this material is given by the fact that graphene nanosheets can be used as carriers for biomolecule delivery to the central nervous system. In this case, an important aspect is the evaluation of their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. Furthermore, graphene can be exploited as a substrate for tissue engineering. In this application, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation.
This chapter discusses the engineering of graphene nanosheets able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. Moreover, the use of graphene to develop three-dimensional scaffolds, or as a component of hybrid composites/multi-layer organic electronics devices, is described. The need of an accurate theoretical modeling of the interface between graphene and biological material is also addressed, by describing the interaction of graphene with proteins and cell membranes at the nanoscale
Stepping out of the shade: control of neuronal activity by the scaffold protein Kidins220/ARMS
No full textThe correct functioning of the nervous system depends on the exquisitely fine control of neuronal excitability and synaptic plasticity, which relies on an intricate network of protein-protein interactions and signaling that shapes neuronal homeostasis during development and in adulthood. In this complex scenario, Kinase D interacting substrate of 220 kDa / ankyrin repeat-rich membrane spanning (Kidins220/ARMS) is a multi-functional scaffold protein preferentially expressed in the nervous system. Engaged in a plethora of interactions with membrane receptors, cytosolic signaling components and cytoskeletal proteins, Kidins220/ARMS is implicated in numerous cellular functions including neuronal survival, neurite outgrowth and maturation and neuronal activity, often in the context of neurotrophin signaling pathways. Recent studies have highlighted a number of cell- and context-specific roles for this protein in the control of synaptic transmission and neuronal excitability, which are at present far from being completely understood. In addition, some evidence has began to emerge, linking alterations of Kidins220 expression to the onset of various neurodegenerative diseases and neuropsychiatric disorders. In this review, we present a concise summary of our fragmentary knowledge of Kidins220/ARMS biological functions, focusing on the mechanism(s) by which it controls various aspects of neuronal activity. We have tried, where possible, to discuss the available evidence in the wider context of neurotrophin-mediated regulation, and to outline emerging roles of Kidins220/ARMS in human pathologies
- …
