scholarly journals Sacsin Deletion Induces Aggregation of Glial Intermediate Filaments

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 299
Author(s):  
Fernanda Murtinheira ◽  
Mafalda Migueis ◽  
Ricardo Letra-Vilela ◽  
Mickael Diallo ◽  
Andrea Quezada ◽  
...  
Keyword(s):  
Intermediate Filaments ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Axonal Neuropathy ◽  
Sensory Neuropathy ◽  
Alexander Disease ◽  
Rat Glioma ◽  
Progressive Cerebellar Ataxia ◽  
Inflammatory Stimuli

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder commonly diagnosed in infants and characterized by progressive cerebellar ataxia, spasticity, motor sensory neuropathy and axonal demyelination. ARSACS is caused by mutations in the SACS gene that lead to truncated or defective forms of the 520 kDa multidomain protein, sacsin. Sacsin function is exclusively studied on neuronal cells, where it regulates mitochondrial network organization and facilitates the normal polymerization of neuronal intermediate filaments (i.e., neurofilaments and vimentin). Here, we show that sacsin is also highly expressed in astrocytes, C6 rat glioma cells and N9 mouse microglia. Sacsin knockout in C6 cells (C6Sacs−/−) induced the accumulation of the glial intermediate filaments glial fibrillary acidic protein (GFAP), nestin and vimentin in the juxtanuclear area, and a concomitant depletion of mitochondria. C6Sacs−/− cells showed impaired responses to oxidative challenges (Rotenone) and inflammatory stimuli (Interleukin-6). GFAP aggregation is also associated with other neurodegenerative conditions diagnosed in infants, such as Alexander disease or Giant Axonal Neuropathy. Our results, and the similarities between these disorders, reinforce the possible connection between ARSACS and intermediate filament-associated diseases and point to a potential role of glia in ARSACS pathology.

scholarly journals Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton

2009 ◽  
Vol 83 (14) ◽  
pp. 7015-7028 ◽  
Author(s):  
Matthew S. Miller ◽  
Laura Hertel
Keyword(s):  
Intermediate Filaments ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Initial Phase ◽  
Axonal Neuropathy ◽  
Cell Tropism ◽  
Giant Axonal Neuropathy ◽  
Cmv Infection ◽  
Viral Particles

ABSTRACT Like all viruses, herpesviruses extensively interact with the host cytoskeleton during entry. While microtubules and microfilaments appear to facilitate viral capsid transport toward the nucleus, evidence for a role of intermediate filaments in herpesvirus entry is lacking. Here, we examined the function of vimentin intermediate filaments in fibroblasts during the initial phase of infection of two genotypically distinct strains of human cytomegalovirus (CMV), one with narrow (AD169) and one with broad (TB40/E) cell tropism. Chemical disruption of the vimentin network with acrylamide, intermediate filament bundling in cells from a patient with giant axonal neuropathy, and absence of vimentin in fibroblasts from vimentin−/− mice severely reduced entry of either strain. In vimentin null cells, viral particles remained in the cytoplasm longer than in vimentin+/+ cells. TB40/E infection was consistently slower than that of AD169 and was more negatively affected by the disruption or absence of vimentin. These findings demonstrate that an intact vimentin network is required for CMV infection onset, that intermediate filaments may function during viral entry to facilitate capsid trafficking and/or docking to the nuclear envelope, and that maintenance of a broader cell tropism is associated with a higher degree of dependence on the vimentin cytoskeleton.

scholarly journals TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Maria-Letizia Campanari ◽  
Anca Marian ◽  
Sorana Ciura ◽  
Edor Kabashi
Keyword(s):  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Dna Binding Protein ◽  
Limiting Factor ◽  
Loss Of Function ◽  
Function Model ◽  
Vertebrate Model ◽  
Ache Expression ◽  
Lateral Sclerosis

The “distal axonopathy” hypothesis in amyotrophic lateral sclerosis (ALS) proposes that pathological changes occur at the neuromuscular junction (NMJ) early in the disease. While acetylcholinesterase (AChE) plays an important role in the functionality of the NMJ, its potential role in ALS remains unexplored. Here, we identified AChE as a limiting factor regulating muscle/motor neuron connection in a vertebrate model of ALS. Knockdown of the TAR DNA-binding protein 43 (TDP-43) orthologue in zebrafish resulted in early defects of motor functions coupled with NMJ disassembly. We found that a partially depleted tdp-43 caused a decrease of ache expression. Importantly, human AChE overexpression reduced the phenotypic defects in the tdp-43 loss of function model, with amelioration of post- and pre-synaptic deficits at the NMJ. In conclusion, our results provide a better understanding of the role of TDP-43 in the NMJ organization and indicate AChE as a contributing factor in the pathology of ALS. In particular, it may be implicated in the early defects that characterize NMJs in this major neurodegenerative disorder.

scholarly journals The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

2021 ◽  
Author(s):  
Gilbert Ogunmokun ◽  
Saikat Dewanjee ◽  
Pratik Chakraborty ◽  
Chandrasekhar Valupadas ◽  
Anupama Chaudhary ◽  
...  
Keyword(s):  
Growth Factors ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Protective Role ◽  
Neuronal Function ◽  
Cytokines And Chemokines ◽  
Glycation End Products ◽  
Gradual Decay ◽  
Shed Light

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

scholarly journals The effect of insomnia on development of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Shaghayegh Sadeghmousavi ◽  
Mahsa Eskian ◽  
Farzaneh Rahmani ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Memory Deficits ◽  
Information Recall ◽  
Important Health ◽  
Important Health Issue

Abstract Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

scholarly journals The regenerating protein 3A: a crucial molecular with dual roles in cancer

2021 ◽  
Author(s):  
Liying Wang ◽  
Yanchun Quan ◽  
Yanxi Zhu ◽  
Xiaoli Xie ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tissue Repair ◽  
Potential Role ◽  
Data Organization ◽  
Dual Roles ◽  
The Third ◽  
The Past ◽  
Inflammatory Stimuli ◽  
Regulation Function

Abstract Introduction REG3A, a member of the third subclass of the Reg family, has been found in a variety of tissues but is not detected in immune cells. In the past decade, it has been determined that REG3A expression is regulated by injury, infection, inflammatory stimuli, and pro-cytokines via different signaling pathways, and it acts as a tissue-repair, bactericidal, and anti-inflammatory molecule in human diseases. Recently, the role of REG3A in cancer has received increasing attention. The present article aims to investigate the structure, expression, regulation, function of REG3A, and to highlight the potential role of REG3A in tumors. Methods A detailed literature search and data organization were conducted to find information about the role of REG3A in variety of physiological functions and tumors. Results Contradictory roles of REG3A have been reported in different tumor models. Some studies have demonstrated that high expression of REG3A in cancers can be oncogenic. Other studies have shown decreased REG3A expression in cancer cells as well as suppressed tumor growth. Conclusions Taken together, better understanding of REG3A may lead to new insights that make it a potentially useful target for cancer therapy.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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