Intrinsic Control of Axon Regeneration

Neuron, Год журнала: 2016, Номер 90(3), С. 437 - 451

Опубликована: Май 1, 2016

Язык: Английский

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JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Microbiology and Molecular Biology Reviews, Год журнала: 2016, Номер 80(3), С. 793 - 835

Опубликована: Июль 28, 2016

SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, embryonic development, via their impact on gene expression, cytoskeletal dynamics, death/survival pathways. Although JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple partners underlying diversity actions. Here we review current knowledge structure isoforms well partnerships intracellular proteins. Many these proteins are direct substrates JNKs. We analyzed almost 100 target in detail within framework classification based regulation by Examples include diverse assortment nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic involved cytoskeleton (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), membrane receptors (BMPR2), mitochondrial (Mcl1, Bim). In addition, because upstream signaling components activity, critically assessed involvement scaffolds roles feedback mechanisms pathway. Despite clarification many regulatory events JNK-dependent during past decade, other structural mechanistic insights just beginning be revealed. These advances open new opportunities understand role pathophysiological states.

Язык: Английский

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CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons

Neuron, Год журнала: 2019, Номер 104(2), С. 239 - 255.e12

Опубликована: Авг. 15, 2019

Highlights•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival uncover genes essential neurons, but not iPSCs or cancer cells•Single-cell RNA-seq reveal distinct neuronal roles ubiquitous genes•Arrayed high-content controlling morphologySummaryCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based were conducted lines rather than healthy, differentiated cells. Here, we describe a (CRISPRi)-based neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous such present results three complementary screens. First, survival-based screen revealed neuron-specific that improved survival upon knockdown. Second, with single-cell transcriptomic readout uncovered several examples whose had strikingly cell-type-specific consequences. Third, longitudinal imaging detected consequences gene on morphology. Our highlight the power unbiased types provide systematic interrogation normal disease states neurons.Video Abstract/cms/asset/c2672569-5397-4e97-a52a-74b50c33ac04/mmc10.mp4Loading ...Download video (mp4, 134 MB)Graphical abstract

Язык: Английский

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Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism

Neuron, Год журнала: 2016, Номер 89(3), С. 449 - 460

Опубликована: Фев. 1, 2016

Язык: Английский

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Axon–soma communication in neuronal injury

Nature reviews. Neuroscience, Год журнала: 2013, Номер 15(1), С. 32 - 42

Опубликована: Дек. 11, 2013

Язык: Английский

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Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia

Nature Neuroscience, Год журнала: 2020, Номер 23(8), С. 927 - 938

Опубликована: Июнь 8, 2020

Язык: Английский

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BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

Progress in Retinal and Eye Research, Год журнала: 2017, Номер 57, С. 1 - 25

Опубликована: Янв. 5, 2017

Язык: Английский

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Apoptotic cell death regulation in neurons

FEBS Journal, Год журнала: 2019, Номер 286(17), С. 3276 - 3298

Опубликована: Июнь 23, 2019

Apoptosis plays a major role in shaping the developing nervous system during embryogenesis as neuronal precursors differentiate to become post‐mitotic neurons. However, once neurons are incorporated into functional circuits and mature, they greatly restrict their capacity die via apoptosis, thus allowing mature persist healthy state throughout life. This robust restriction of apoptotic pathway differentiation maturation is defined by multiple unique mechanisms that function more precisely control intrinsic pathway. while these necessary for survival, still capable activating certain pathological contexts. In this review, we highlight key governing survival neurons, also detailing physiological contexts which overcoming high threshold.

Язык: Английский

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MAPK-Activated Protein Kinases: Servant or Partner?

Annual Review of Biochemistry, Год журнала: 2022, Номер 91(1), С. 505 - 540

Опубликована: Март 19, 2022

Mitogen-activated protein kinase (MAPK)-activated kinases (MAPKAPKs) are defined by their exclusive activation MAPKs. They can be activated classical and atypical MAPKs that have been stimulated mitogens various stresses. Genetic deletions of MAPKAPKs availability highly specific small-molecule inhibitors continuously increased our functional understanding these kinases. cooperate in the regulation gene expression at level transcription; RNA processing, export, stability; synthesis. The diversity stimuli for MAPK activation, crosstalk between different MAPKAPKs, substrate pattern orchestrate immediate-early inflammatory responses space time ensure proper control cell growth, differentiation, behavior. Hence, promising targets cancer therapy treatments conditions acute chronic inflammation, such as cytokine storms rheumatoid arthritis.

Язык: Английский

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The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review

Biomolecules, Год журнала: 2024, Номер 14(2), С. 243 - 243

Опубликована: Фев. 19, 2024

JNK is named after c-Jun N-terminal kinase, as it responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, also known stress-activated (SAPK) because can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, regulates various cell behaviors such differentiation, proliferation, survival, metabolic reprogramming. Dysregulated signaling contributes to several types human diseases. Although role pathway in single disease has been summarized previous publications, comprehensive review its multiple kinds diseases missing. In this review, we begin introducing landmark discoveries, structures, tissue expression, activation mechanisms pathway. Next, come focus work: summary deregulated Beyond that, discuss current strategies targeting therapeutic intervention summarize application inhibitors well challenges now faced. We expect that provide more insight into critical pathogenesis hope provides important clues ameliorating conditions.

Язык: Английский

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