Understanding axon guidance: are we nearly there yet?

Development, Journal Year: 2018, Volume and Issue: 145(10)

Published: May 14, 2018

During nervous system development, neurons extend axons to reach their targets and form functional circuits. The faulty assembly or disintegration of such circuits results in disorders the system. Thus, understanding molecular mechanisms that guide lead neural circuit formation is interest not only developmental neuroscientists but also for a better comprehension disorders. Recent studies have demonstrated how crosstalk between different families guidance receptors can regulate axonal navigation at choice points, changes growth cone behaviour intermediate require surface expression receptors. These be achieved by variety mechanisms, including transcription, translation, protein-protein interactions, specific trafficking proteins mRNAs. Here, I review these axon highlighting most recent advances field challenge textbook model guidance.

Language: Английский

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Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders

Progress in Neurobiology, Journal Year: 2019, Volume and Issue: 185, P. 101732 - 101732

Published: Dec. 6, 2019

Circulating microRNAs (cimiRNAs) are a class of non-encoding RNAs found in bodily fluids such as blood, cerebrospinal fluid (CSF) and tears. CimiRNAs have been implicated promising biomarkers for central nervous system (CNS) disorders because they actively secreted messengers profoundly involved fine-tuning developmental differentiation processes. Furthermore, attractive extremely stable, tissue enriched can be determined quantitative manner. This review aims to provide comprehensive assessment on the current progress regarding potential value cimiRNAs CNS biomarkers. Within this framework five explored which share common pathological hallmark namely cognitive impairment. The include Major depression disorder (MDD), Bipolar (BD), Schizophrenia (SZ), Alzheimer's disease (AD) Parkinson (PD). similarities differences between altered different described. miR-29 family, miR-34a-5p miR-132-3p discussed dysregulated disorders. it is shown that type used measuring important inconsistencies expression directions when comparing CSF, blood cell-free cell-bound samples.

Language: Английский

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Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(23), P. 6055 - 6055

Published: Nov. 30, 2019

MicroRNAs are post-transcriptional regulators of gene expression, crucial for neuronal differentiation, survival, and activity. Age-related dysregulation microRNA biogenesis increases vulnerability to cellular stress may contribute the development progression neurodegenerative diseases. All major disorders also associated with oxidative stress, which is widely recognized as a potential target protective therapies. Albeit often considered separately, networks inextricably entwined in processes. Oxidative affects expression levels multiple microRNAs and, conversely, regulate many genes involved an response. Both regulatory influence other processes linked neurodegeneration, such mitochondrial dysfunction, deregulation proteostasis, increased neuroinflammation, ultimately lead death. Modulating relatively small number therefore alleviate pathological damage have neuroprotective Here, we review role individual related pathways four conditions: Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD) disease, amyotrophic lateral sclerosis (ALS). We discuss problems use oversimplified models highlight perspectives studying regulation human stem cell-derived neurons.

Language: Английский

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SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: March 31, 2021

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties both classical TFs and architectural components chromatin. Since cloning Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players regulation multiple developmental physiological processes. govern diverse cellular processes during development, such maintaining pluripotency stem cells, cell proliferation, fate decisions/germ layer formation well terminal differentiation into tissues organs. However, are not limited development since influence survival, regeneration, death control homeostasis adult tissues. This review summarized current knowledge central nervous system development. Some suspend neural progenitors proliferative, stem-like state prevent differentiation. function pioneer occupy silenced target genes keep them a poised for activation at subsequent stages At appropriate stage members maintain stemness down-regulated cells competent differentiate, while other take over functions process Distinct determine down-stream neuronal glial Thus, sequentially acting orchestrate lineage defining phenotypes. In line with crucial deregulation specific activities is associated neurodevelopmental disorders (NDDs). overview about link between gene variants NDDs presented. We outline neurogenesis brain discuss whether impaired neurogenesis, detected neurodegenerative diseases, could be activities. present data regarding interaction signaling pathways microRNAs play Finally, future research directions will improve distinct various health diseases presented discussed.

Language: Английский

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Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF

Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112063 - 112063

Published: Feb. 1, 2023

Extracellular vesicles (EVs) have emerged as mediators of cellular communication, in part via the delivery associated microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. We show brain-derived neurotrophic factor (BDNF) mediates sorting miR-132-5p, miR-218-5p, and miR-690 neuron-derived EVs. BDNF-induced EVs turn increase excitatory synapse formation recipient hippocampal neurons, which is dependent on inter-neuronal these miRNAs. Transcriptomic analysis further indicates differential expression developmental synaptogenesis-related genes by EVs, many are predicted targets miR-690. Furthermore, up-regulate synaptic vesicle (SV) clustering a transmissible manner, thereby increasing transmission synchronous neuronal activity. As BDNF EV-miRNAs miR-218 miR-132 were previously implicated neuropsychiatric disorders such anxiety depression, our results contribute to better understanding characterized aberrant neural circuit connectivity.

Language: Английский

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Molecular profile of bladder cancer progression to clinically aggressive subtypes

Nature Reviews Urology, Journal Year: 2024, Volume and Issue: 21(7), P. 391 - 405

Published: Feb. 6, 2024

Language: Английский

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Autism spectrum disorder: insights into convergent mechanisms from transcriptomics

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 20(1), P. 51 - 63

Published: Nov. 2, 2018

Language: Английский

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Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

Cells, Journal Year: 2020, Volume and Issue: 9(8), P. 1837 - 1837

Published: Aug. 5, 2020

Schizophrenia is a severe psychiatric disorder with complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has strong genetic component, heritability around 80%, there also range environmental exposures stressors have been implicated disease development neuropathology, such as maternal immune infection, obstetric complications, childhood trauma cannabis exposure. It postulated epigenetic factors, well regulatory non-coding RNAs, mediate the effects these stressors. In this review, we explore most well-known marks, including DNA methylation histone modification, along emerging RNA mediators epigenomic state, miRNAs lncRNAs, discuss their collective potential for involvement pathophysiology through postmortem analysis brain tissue. Given peripheral tissues, blood, saliva, olfactory epithelium same composition are exposed to many exposures, examine some studies supporting application tissues biomarker discovery schizophrenia. Finally, provide perspective on how biomarkers may be utilized capture signature past events informs future treatment.

Language: Английский

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Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease

Biomolecules, Journal Year: 2021, Volume and Issue: 11(1), P. 75 - 75

Published: Jan. 8, 2021

Rett Syndrome (RTT) is a severe, rare, and progressive developmental disorder with patients displaying neurological regression autism spectrum features. The affected individuals are primarily young females, more than 95% of carry de novo mutation(s) in the Methyl-CpG-Binding Protein 2 (MECP2) gene. While majority RTT have MECP2 mutations (classical RTT), small fraction (atypical RTT) may genetic other genes such as cyclin-dependent kinase-like 5 (CDKL5) FOXG1. Due to basis symptoms, MeCP2 function was originally studied nerve cells (neurons). However, later research highlighted its importance cell types brain including glia. In this regard, scientists benefitted from modeling disease using many different cellular systems transgenic mice loss- or gain-of-function mutations. Additionally, limited human postmortem tissues provided invaluable findings pathobiology mechanism. expression tightly regulated, altered leads abnormal function, implicating some cases disorders. certain conditions, homeostasis control impaired, regulation which rodents involves regulatory microRNA (miR132) brain-derived neurotrophic factor (BDNF). Here, we will provide an overview recent advances understanding underlying mechanism associated gene along disease, role two most protein variants (MeCP2E1 MeCP2E2 isoforms), mechanisms that network brain, BDNF miR132.

Language: Английский

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Non-coding RNA in the wiring and remodeling of neural circuits

Neuron, Journal Year: 2023, Volume and Issue: 111(14), P. 2140 - 2154

Published: May 24, 2023

Language: Английский

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