Inhibition of extracellular regulated kinase (ERK)-1/2 signaling pathway in the prevention of ALS: Target inhibitors and influences on neurological dysfunctions

European Journal of Cell Biology, Journal Year: 2021, Volume and Issue: 100(7-8), P. 151179 - 151179

Published: Sept. 1, 2021

Cell signal transduction pathways are essential modulators of several physiological and pathological processes in the brain. During overactivation, these signaling may lead to disease progression. Abnormal protein kinase activation is associated with biological dysfunctions that facilitate neurodegeneration under different conditions. As a result, understanding brain disorders' development or Recent research findings indicate crucial role extracellular signal-regulated kinase-1/2 (ERK-1/2) during neuronal process. ERK-1/2 key component its mitogen-activated (MAPK) group, controlling certain neurological activities by regulating metabolic pathways, cell proliferation, differentiation, apoptosis. also influences elastic properties, nerve growth, cognitive processing injuries. The primary goal this review elucidate ERK1/2 signaling, which involved ALS-related neuropathological dysfunctions. ALS rare disorder category mainly affects cells responsible for voluntary muscle activity. progressive, means symptoms getting worse over time, there no cure effective treatment avoid reverse. Genetic abnormalities, oligodendrocyte degradation, glial immune deregulation Furthermore, current identifies inhibitors can promote neuroprotection neurotrophic effects against clinical-pathological presentation ALS. future, potential could be used related neurocomplications.

Language: Английский

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G protein-coupled receptor kinase-2 (GRK-2) controls exploration through neuropeptide signaling in Caenorhabditis elegans

PLoS Genetics, Journal Year: 2023, Volume and Issue: 19(1), P. e1010613 - e1010613

Published: Jan. 18, 2023

Animals alter their behavior in manners that depend on environmental conditions as well developmental and metabolic states. For example, C . elegans is quiescent during larval molts or of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined a lack body movement), the expression additional locomotor states are associated with increased reduced locomotion activity, such roaming (exploration behavior) dwelling (local search). Here we find enhanced, G protein-coupled receptor kinase grk-2 mutant animals. was previously shown to act chemosensation, locomotion, egg-laying behaviors. Using neuron-specific rescuing experiments, show GRK-2 acts multiple ciliated chemosensory neurons control behavior. opposite ways cGMP-dependent protein gene egl-4 Analysis mutants defects sensory indicates cilium-structure same pathway We controls manner neuropeptide NPR-1 neuropeptides FLP-1 FLP-18. Finally, secretion negatively regulated by overexpression reduces These results define molecular pathways modulate

Language: Английский

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Impairment of the neurotrophic signaling hub B-Raf contributes to motoneuron degeneration in spinal muscular atrophy

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(18)

Published: April 30, 2021

Significance The mechanisms of neurodegeneration are important targets for future treatments the devastating motoneuron disease spinal muscular atrophy (SMA). Here, we show an altered signaling network in SMA models and patient cells with a reduced B-Raf expression center. is crucial survival, present data that restoration ameliorates loss symptoms models.

Language: Английский

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Antibacterial peptides from Monochamus alternatus induced oxidative stress and reproductive defects in pine wood nematode through the ERK/MAPK signaling pathway

Pesticide Biochemistry and Physiology, Journal Year: 2023, Volume and Issue: 194, P. 105511 - 105511

Published: June 28, 2023

Language: Английский

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Dynamic neurotransmitter specific transcription factor expression profiles during Drosophila development

Biology Open, Journal Year: 2020, Volume and Issue: 9(5)

Published: May 15, 2020

ABSTRACT The remarkable diversity of neurons in the nervous system is generated during development, when properties such as cell morphology, receptor profiles and neurotransmitter identities are specified. In order to gain a greater understanding specification we profiled transcription state cholinergic, GABAergic glutamatergic vivo at three developmental time points. We identified 86 differentially expressed factors that uniquely enriched, or depleted, specific type. Some show similar profile across others only enrichment depletion stages. Profiling Acj6 (cholinergic enriched) Ets65A depleted) binding sites reveals they both directly bind ChAT locus, addition wide spectrum other key neuronal differentiation genes. also cholinergic enriched mostly non-overlapping populations adult brain, implying absence combinatorial regulation fate this context. Furthermore, our data underlines that, Caenorhabditis elegans, there no simple factor codes for type specification. This article has an associated First Person interview with first author paper.

Language: Английский

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Klebsiella aerogenes ingestion elicits behavioral changes and innate immunity in the host, Caenorhabditis elegans

Developmental & Comparative Immunology, Journal Year: 2024, Volume and Issue: 154, P. 105138 - 105138

Published: Jan. 27, 2024

Language: Английский

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Serotonin signals through postsynaptic Gαq, Trio RhoGEF, and diacylglycerol to promote Caenorhabditis elegans egg-laying circuit activity and behavior

Genetics, Journal Year: 2022, Volume and Issue: 221(3)

Published: May 17, 2022

Abstract Activated Gαq signals through phospholipase-Cβ and Trio, a Rho GTPase exchange factor (RhoGEF), but how these distinct effector pathways promote cellular responses to neurotransmitters like serotonin remains poorly understood. We used the egg-laying behavior circuit of Caenorhabditis elegans determine whether Trio mediate signaling independent or related biochemical pathways. Our genetic rescue experiments suggest that functions in neurons while both postsynaptic vulval muscles. While Gαq, phospholipase-Cβ, mutants fail lay eggs response serotonin, optogenetic stimulation serotonin-releasing HSN restores egg laying only mutants. Phospholipase-Cβ showed muscle Ca2+ transients strong had little no activity. Treatment with phorbol 12-myristate 13-acetate mimics 1,2-diacylglycerol, product PIP2 hydrolysis, rescued activity defects mutants, suggesting phospholipase-C synaptic transmission via modulation 1,2-diacylglycerol levels. 1,2-Diacylglycerol activates effectors including UNC-13; however, we find esters, not stimulate unc-13 These results support model where UNC-13 promotes neurotransmitter release, also factor, an unidentified, 13-acetate-responsive excitability. Thus, same neuromodulator can signal cells coordinate activation motor circuit.

Language: Английский

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Schistosoma mansoni excretory-secretory products induce protein kinase signalling, hyperkinesia, and stem cell proliferation in the opposite sex

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Sept. 26, 2023

Adult male and female schistosomes in copula dwell within human blood vessels lay eggs that cause the major Neglected Tropical Disease schistosomiasis. How males females communicate to each other is poorly understood; however, male-female physical interaction known be important. Here, we investigate whether excretory-secretory products (ESPs), released into external milieu by mature Schistosoma mansoni, might induce responses opposite sex. We demonstrate ESPs adhere surface of sex worms inducing activation extracellular signal-regulated kinase (ERK) p38 mitogen-activated protein (p38 MAPK) pathways, particularly parasite tegument. Furthermore, show stimulated signalling juvenile worms. Strikingly, from promote stem cell proliferation, an ERK- MAPK-dependent manner, tegument testes males, ovaries vitellaria females. Hyperkinesia also occurs following ESP exposure. Our findings support hypothesis may over distance modulate key processes underlying worm development disease progression, opening unique avenues for schistosomiasis control.

Language: Английский

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A role for the Erk MAPK pathway in modulating SAX-7/L1CAM-dependent locomotion inCaenorhabditis elegans

Genetics, Journal Year: 2021, Volume and Issue: 220(2)

Published: Nov. 25, 2021

L1CAMs are immunoglobulin cell adhesion molecules that function in nervous system development and function. Besides being associated with autism schizophrenia spectrum disorders, impaired L1CAM also underlies the X-linked L1 syndrome, which encompasses a group of neurological conditions, including spastic paraplegia congenital hydrocephalus. Studies on vertebrate invertebrate established conserved roles include axon guidance, dendrite morphogenesis, synapse development, maintenance neural architecture. We previously identified genetic interaction between Caenorhabditis elegans encoded by sax-7 gene RAB-3, GTPase functions synaptic neurotransmission; rab-3; mutant animals exhibit synthetic locomotion abnormalities neuronal dysfunction. Here, we show this synergism occurs when loss SAX-7 is combined mutants other genes encoding key players vesicle (SV) cycle. In contrast, does not interact synaptogenesis. These findings suggest postdevelopmental role for regulation activity. To assess possibility, conducted electrophysiological recordings ultrastructural analyses at neuromuscular junctions; these did reveal obvious abnormalities. Lastly, based forward screen suppressors phenotypes, determined ERK Mitogen-activated Protein Kinase (MAPK) pathway can suppress defects. Moreover, Erk signaling acts subset cholinergic neurons head to promote coordinated locomotion. combination, results modulatory MAPK L1CAM-dependent C. elegans.

Language: Английский

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Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 841 - 841

Published: April 10, 2024

RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present unique opportunity to delve into intricacies complex neurological disorders. Afflicting approximately one thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with pronounced impact on central and peripheral nervous system. In pursuit understanding RASopathies’ neurobiology establishing phenotype–genotype relationships, vivo non-mammalian models have emerged indispensable tools. Species such Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species Gallus gallus embryos proven be invaluable shedding light intricate pathways implicated RASopathies. Despite some inherent weaknesses, these genetic offer distinct advantages over traditional rodent models, providing holistic perspective genetics, multi-organ involvement, interplay among various pathway components, offering insights pathophysiological aspects mutations-driven symptoms. This review underscores value investigating basis for unraveling underlying mechanisms contributing broader complexities. It also emphasizes pivotal role serving crucial preliminary step development innovative therapeutic strategies.

Language: Английский

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