scholarly journals Myosin XVI in the Nervous System

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1903
Author(s):  
Elek Telek ◽  
András Kengyel ◽  
Beáta Bugyi
Keyword(s):  
Nervous System ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Structural Features ◽  
Neural Cells ◽  
Cellular Functions ◽  
Cytoskeleton Reorganization ◽  
Neural Tissues ◽  
Cell Signaling Pathways

The myosin family is a large inventory of actin-associated motor proteins that participate in a diverse array of cellular functions. Several myosin classes are expressed in neural cells and play important roles in neural functioning. A recently discovered member of the myosin superfamily, the vertebrate-specific myosin XVI (Myo16) class is expressed predominantly in neural tissues and appears to be involved in the development and proper functioning of the nervous system. Accordingly, the alterations of MYO16 has been linked to neurological disorders. Although the role of Myo16 as a generic actin-associated motor is still enigmatic, the N-, and C-terminal extensions that flank the motor domain seem to confer unique structural features and versatile interactions to the protein. Recent biochemical and physiological examinations portray Myo16 as a signal transduction element that integrates cell signaling pathways to actin cytoskeleton reorganization. This review discusses the current knowledge of the structure-function relation of Myo16. In light of its prevalent localization, the emphasis is laid on the neural aspects.

scholarly journals Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1678
Author(s):  
Liriopé Toupenet Marchesi ◽  
Marion Leblanc ◽  
Giovanni Stevanin
Keyword(s):  
Nervous System ◽  
Motor Neurons ◽  
Neurological Disorders ◽  
Hereditary Spastic Paraplegia ◽  
Current Knowledge ◽  
Spastic Paraplegia ◽  
Functional Convergence ◽  
The Common ◽  
Hsp Genes

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Protein kinase CK2: structure, regulation and role in cellular decisions of life and death

2003 ◽  
Vol 369 (1) ◽  
pp. 1-15 ◽  
Author(s):  
David W. LITCHFIELD
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Serine Threonine Kinase ◽  
Life And Death ◽  
Dual Specificity ◽  
Mechanistic Basis ◽  
Kinase Ck2

Protein kinase CK2 ('casein kinase II') has traditionally been classified as a messenger-independent protein serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (α and/or α′) subunits and two regulatory β subunits. Accumulated biochemical and genetic evidence indicates that CK2 has a vast array of candidate physiological targets and participates in a complex series of cellular functions, including the maintenance of cell viability. This review summarizes current knowledge of the structural and enzymic features of CK2, and discusses advances that challenge traditional views of this enzyme. For example, the recent demonstrations that individual CK2 subunits exist outside tetrameric complexes and that CK2 displays dual-specificity kinase activity raises new prospects for the precise elucidation of its regulation and cellular functions. This review also discusses a number of the mechanisms that contribute to the regulation of CK2 in cells, and will highlight emerging insights into the role of CK2 in cellular decisions of life and death. In this latter respect, recent evidence suggests that CK2 can exert an anti-apoptotic role by protecting regulatory proteins from caspase-mediated degradation. The mechanistic basis of the observation that CK2 is essential for viability may reside in part in this ability to protect cellular proteins from caspase action. Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis.

The GCN5: its biological functions and therapeutic potentials

2021 ◽  
Vol 135 (1) ◽  
pp. 231-257
Author(s):  
Md. Ezazul Haque ◽  
Md. Jakaria ◽  
Mahbuba Akther ◽  
Duk-Yeon Cho ◽  
In-Su Kim ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Cellular Proliferation ◽  
Chromatin Modification ◽  
Structural Features ◽  
Histone Acetyltransferases ◽  
Epigenetic Landscape ◽  
General Control ◽  
Wide Range ◽  
Lysine Acetyltransferase

Abstract General control non-depressible 5 (GCN5) or lysine acetyltransferase 2A (KAT2A) is one of the most highly studied histone acetyltransferases. It acts as both histone acetyltransferase (HAT) and lysine acetyltransferase (KAT). As an HAT it plays a pivotal role in the epigenetic landscape and chromatin modification. Besides, GCN5 regulates a wide range of biological events such as gene regulation, cellular proliferation, metabolism and inflammation. Imbalance in the GCN5 activity has been reported in many disorders such as cancer, metabolic disorders, autoimmune disorders and neurological disorders. Therefore, unravelling the role of GCN5 in different diseases progression is a prerequisite for both understanding and developing novel therapeutic agents of these diseases. In this review, we have discussed the structural features, the biological function of GCN5 and the mechanical link with the diseases associated with its imbalance. Moreover, the present GCN5 modulators and their limitations will be presented in a medicinal chemistry perspective.

scholarly journals Store-Operated Calcium Channels in Physiological and Pathological States of the Nervous System

2020 ◽  
Vol 14 ◽  
Author(s):  
Isis Zhang ◽  
Huijuan Hu
Keyword(s):  
Nervous System ◽  
Calcium Channels ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Physiological Role ◽  
The Body ◽  
Store Operated Calcium Entry ◽  
Important Pathway ◽  
Molecular Components

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.

miRNAs in development and pathogenesis of the nervous system

2013 ◽  
Vol 41 (4) ◽  
pp. 815-820 ◽  
Author(s):  
Jakub S. Nowak ◽  
Gracjan Michlewski
Keyword(s):  
Nervous System ◽  
Present Article ◽  
Neurodevelopmental Disorders ◽  
Current Knowledge ◽  
And Function ◽  
Human Nervous System

The human nervous system expresses approximately 70% of all miRNAs (microRNAs). Changing levels of certain ubiquitous and brain-specific miRNAs shape the development and function of the nervous system. It is becoming clear that misexpression of some miRNAs can contribute towards neurodevelopmental disorders. In the present article, we review the current knowledge of the role of miRNAs in development and pathogenesis of the nervous system.

scholarly journals POLIII-derived non-coding RNAs acting as scaffolds and decoys

2019 ◽  
Vol 11 (10) ◽  
pp. 880-885 ◽  
Author(s):  
Hendrik Täuber ◽  
Stefan Hüttelmaier ◽  
Marcel Köhn
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Control Of Gene Expression ◽  
Ribonucleoprotein Complexes ◽  
Small Ncrnas ◽  
Non Coding Rnas ◽  
And Function

Abstract A large variety of eukaryotic small structured POLIII-derived non-coding RNAs (ncRNAs) have been described in the past. However, for only few, e.g. 7SL and H1/MRP families, cellular functions are well understood. For the vast majority of these transcripts, cellular functions remain unknown. Recent findings on the role of Y RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes (RNPs). These RNPs provide cellular `machineries’, which are essential for guiding the fate and function of a variety of RNAs. In this review, we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of RNPs. We propose that these ncRNAs serve as scaffolding factors that `chaperone’ RNA-binding proteins (RBPs) to form functional RNPs. In addition or associated with this role, some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA substrates. This suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and lncRNAs.

scholarly journals BDNF signaling during the lifetime of dendritic spines

2020 ◽  
Vol 382 (1) ◽  
pp. 185-199 ◽  
Author(s):  
Marta Zagrebelsky ◽  
Charlotte Tacke ◽  
Martin Korte
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Conclusive Evidence ◽  
Excitatory Synapses ◽  
Neuronal Homeostasis ◽  
Bdnf Signaling ◽  
Spine Number

Abstract Dendritic spines are tiny membrane specialization forming the postsynaptic part of most excitatory synapses. They have been suggested to play a crucial role in regulating synaptic transmission during development and in adult learning processes. Changes in their number, size, and shape are correlated with processes of structural synaptic plasticity and learning and memory and also with neurodegenerative diseases, when spines are lost. Thus, their alterations can correlate with neuronal homeostasis, but also with dysfunction in several neurological disorders characterized by cognitive impairment. Therefore, it is important to understand how different stages in the life of a dendritic spine, including formation, maturation, and plasticity, are strictly regulated. In this context, brain-derived neurotrophic factor (BDNF), belonging to the NGF-neurotrophin family, is among the most intensively investigated molecule. This review would like to report the current knowledge regarding the role of BDNF in regulating dendritic spine number, structure, and plasticity concentrating especially on its signaling via its two often functionally antagonistic receptors, TrkB and p75NTR. In addition, we point out a series of open points in which, while the role of BDNF signaling is extremely likely conclusive, evidence is still missing.

scholarly journals Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Bollaerts ◽  
Jessie Van houcke ◽  
Lien Andries ◽  
Lies De Groef ◽  
Lieve Moons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Current Knowledge ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

scholarly journals Generation of protein kinase Ck1α mutants which discriminate between canonical and non-canonical substrates

2005 ◽  
Vol 391 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Victor H. Bustos ◽  
Oriano Marin ◽  
Flavio Meggio ◽  
Luca Cesaro ◽  
Catherine C. Allende ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Structural Features ◽  
Side Chain ◽  
Cellular Functions ◽  
Peptide Substrates ◽  
Triple Mutation ◽  
Alanine Scan ◽  
Lysine Residues ◽  
The Individual

Protein kinase CK1 denotes a family of pleiotropic serine/threonine protein kinases implicated in a variety of cellular functions. Typically, CK1 acts as a ‘phosphate-directed’ kinase whose targeting is primed by a single phosphorylated side chain at position n−3 or n−4 relative to serine/threonine, but increasing evidence is accumulating that CK1 can also engage some of its substrates at sites that do not conform to this canonical consensus. In the present paper, we show that CK1α phosphorylates with the same efficiency phosphopeptides primed by a phosphoserine residue at either n−3 [pS(−3)] or n−4 [pS(−4)] positions. The phosphorylation efficiency of the pS(−4) peptide, and to a lesser extent that of the pS(−3) peptide, is impaired by the triple mutation of the lysine residues in the K229KQK232 stretch to alanine residues, promoting 40-fold and 6-fold increases of Km respectively. In both cases, the individual mutation of Lys232 is as detrimental as the triple mutation. A kinetic alanine-scan analysis with a series of substituted peptide substrates in which the priming phosphoserine residue was effectively replaced by a cluster of four aspartate residues was also consistent with a crucial role of Lys232 in the recognition of the acidic determinant at position n−4. In sharp contrast, the phosphorylation of β-catenin and of a peptide including the non-canonical β-catenin site (Ser45) lacking acidic/phosphorylated determinants upstream is not significantly affected by mutations in the KKQK stretch. These data provide a molecular insight into the structural features that underlie the site specificity of CK1α and disclose the possibility of developing strategies for the preferential targeting of subsets of CK1 substrates.

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