scholarly journals Reelin in the Years: Controlling Neuronal Migration and Maturation in the Mammalian Brain

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Gabriella D'Arcangelo
Keyword(s):  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Adult Brain ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Layer Formation ◽  
Essential Factor ◽  
Multifunctional Protein ◽  
And Function

The extracellular protein Reelin was initially identified as an essential factor in the control of neuronal migration and layer formation in the developing mammalian brain. In the years following its discovery, however, it became clear that Reelin is a multifunctional protein that controls not only the positioning of neurons in the developing brain, but also their growth, maturation, and synaptic activity in the adult brain. In this review, we will highlight the major discoveries of the biological activities of Reelin and the underlying molecular mechanisms that affect the development and function of the mammalian brain, from embryonic ages to adulthood.

scholarly journals The Expression and Distributions of ANP32A in the Developing Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shanshan Wang ◽  
Yunliang Wang ◽  
Qingshan Lu ◽  
Xinshan Liu ◽  
Fuyu Wang ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Fetal Brain ◽  
Tissue Expression ◽  
Developing Brain ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Growing Up ◽  
Embryonic Mouse ◽  
And Function

Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has multiple functions involved in neuritogenesis, transcriptional regulation, and apoptosis. However, whether ANP32A has an effect on the mammalian developing brain is still in question. In this study, it was shown that brain was the organ that expressed the most abundant ANP32A by human multiple tissue expression (MTE) array. The distribution of ANP32A in the different adult brain areas was diverse dramatically, with high expression in cerebellum, temporal lobe, and cerebral cortex and with low expression in pons, medulla oblongata, and spinal cord. The expression of ANP32A was higher in the adult brain than in the fetal brain of not only humans but also mice in a time-dependent manner. ANP32A signals were dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in the granular layer of the cerebellum and the cerebral cortex when the mice were growing up, as well as in the Purkinje cells of the cerebellum. The variation of expression levels and distribution of ANP32A in the developing brain would imply that ANP32A may play an important role in mammalian brain development, especially in the differentiation and function of neurons in the cerebellum and the cerebral cortex.

Age-related changes in microglial physiology: the role for healthy brain ageing and neurodegenerative disorders

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Olga Garaschuk
Keyword(s):  
Neurodegenerative Disorders ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Brain Parenchyma ◽  
Immune Defense ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Age Related ◽  
Brain Ageing ◽  
The Brain

AbstractMicroglia are the main immune cells of the brain contributing, however, not only to brain’s immune defense but also to many basic housekeeping functions such as development and maintenance of functional neural networks, provision of trophic support for surrounding neurons, monitoring and modulating the levels of synaptic activity, cleaning of accumulating extracellular debris and repairing microdamages of the brain parenchyma. As a consequence, age-related alterations in microglial function likely have a manifold impact on brain’s physiology. In this review, I discuss the recent data about physiological properties of microglia in the adult mammalian brain; changes observed in the brain innate immune system during healthy aging and the probable biological mechanisms responsible for them as well as changes occurring in humans and mice during age-related neurodegenerative disorders along with underlying cellular/molecular mechanisms. Together these data provide a new conceptual framework for thinking about the role of microglia in the context of age-mediated brain dysfunction.

scholarly journals Tight Regulation of Major Histocompatibility Complex I for the Spatial and Temporal Expression in the Hippocampal Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuqing Shen ◽  
Jianqiong Zhang
Keyword(s):  
Major Histocompatibility Complex ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Class I ◽  
Major Histocompatibility ◽  
Temporal Expression ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
And Function

The expression and function of immune molecules, such as major histocompatibility complex (MHC), within the developing and adult brain have been discovered over the past few years. Studies utilizing classical class I MHC knockout animals suggest that these molecules, in fact, play essential roles in the establishment, function, and modification of synapses in the CNS. Altered neuronal expression of class I MHC, as has been reported in pathological conditions, leads to aberrations in neuronal development and repair. In the hippocampus, cellular and molecular mechanisms that regulate synaptic plasticity have heretofore been extensively studied. It is for this reason that multiple studies directed at better understanding the expression, regulation, and function of class I MHC within the hippocampus have been undertaken. Since several previous reviews have addressed the roles of class I MHC in the formation and function of hippocampal connections, the present review will focus on describing the spatial and temporal expression of class I MHC in developing, healthy adult, and aging hippocampus. Herein, we also review current literatures exploring mechanisms that regulate class I MHC expression in murine hippocampus. With this review, we aim to facilitate a deeper mechanistic understanding into the complex tight regulation of MHC I expression in hippocampus, which are needed as we explore the potential for targeting MHC I for therapeutic intervention in normal aging and in neurodegenerative diseases in the future.

scholarly journals Mechanisms of Long Non-Coding RNAs in Cancers and Their Dynamic Regulations

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1245 ◽  
Author(s):  
Xiao-Zhen Zhang ◽  
Hao Liu ◽  
Su-Ren Chen
Keyword(s):  
Noncoding Rna ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Cancer Therapies ◽  
Search Terms ◽  
Non Coding Rna ◽  
Pubmed Database ◽  
And Function ◽  
Long Non Coding Rna

Long non-coding RNA (lncRNA), which is a kind of noncoding RNA, is generally characterized as being more than 200 nucleotide transcripts in length. LncRNAs exhibit many biological activities, including, but not limited to, cancer development. In this review, a search of the PubMed database was performed to identify relevant studies published in English. The term “lncRNA or long non-coding RNA” was combined with a range of search terms related to the core focus of the review: mechanism, structure, regulation, and cancer. The eligibility of the retrieved studies was mainly based on the abstract. The decision as to whether or not the study was included in this review was made after a careful assessment of its content. The reference lists were also checked to identify any other study that could be relevant to this review. We first summarized the molecular mechanisms of lncRNAs in tumorigenesis, including competing endogenous RNA (ceRNA) mechanisms, epigenetic regulation, decoy and scaffold mechanisms, mRNA and protein stability regulation, transcriptional and translational regulation, miRNA processing regulation, and the architectural role of lncRNAs, which will help a broad audience better understand how lncRNAs work in cancer. Second, we introduced recent studies to elucidate the structure of lncRNAs, as there is a link between lncRNA structure and function and visualizing the architectural domains of lncRNAs is vital to understanding their function. Third, we explored emerging evidence for regulators of lncRNA expression, lncRNA turnover, and lncRNA modifications (including 5-methylcytidine, N6-methyladenosine, and adenosine to inosine editing), highlighting the dynamics of lncRNAs. Finally, we used autophagy in cancer as an example to interpret the diverse mechanisms of lncRNAs and introduced clinical trials of lncRNA-based cancer therapies.

scholarly journals Regulation of Reelin functions by specific proteolytic processing in the brain

2021 ◽  
Author(s):  
Mitsuharu Hattori ◽  
Takao Kohno
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Proteolytic Processing ◽  
Postnatal Brain ◽  
Dendrite Development ◽  
Mature Brain ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
The Brain

Abstract The secreted glycoprotein Reelin plays important roles in both brain development and function. During development, Reelin regulates neuronal migration and dendrite development. In the mature brain, the glycoprotein is involved in synaptogenesis and synaptic plasticity. It has been suggested that Reelin loss or decreased function contributes to the onset and/or deterioration of neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease. While the molecular mechanisms underpinning Reelin function remain unclear, recent studies have suggested that the specific proteolytic cleavage of Reelin may play central roles in the embryonic and postnatal brain. In this review, we focus on Reelin proteolytic processing and review its potential physiological roles.

scholarly journals Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

2021 ◽  
Author(s):  
Agnieszka Wnuk ◽  
Małgorzata Kajta
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Cells ◽  
Industrial Applications ◽  
Mammalian Brain ◽  
Human Environment ◽  
Developmental Abnormalities ◽  
Increased Risk ◽  
Wide Range ◽  
And Function

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

Environment and Brain Plasticity: Towards an Endogenous Pharmacotherapy

2014 ◽  
Vol 94 (1) ◽  
pp. 189-234 ◽  
Author(s):  
Alessandro Sale ◽  
Nicoletta Berardi ◽  
Lamberto Maffei
Keyword(s):  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Brain Plasticity ◽  
System Development ◽  
Basic Research ◽  
Nervous System Development ◽  
Adult Brain ◽  
Aging Brain ◽  
Cerebral Neurons ◽  
And Function

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.

scholarly journals Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Gabby Rudenko
Keyword(s):  
Information Transfer ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Scale Up ◽  
Autism Spectrum ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Synaptic Membrane ◽  
Protein Partners

Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming trans-complexes spanning the synaptic cleft or cis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

Rheb in neuronal degeneration, regeneration, and connectivity

2017 ◽  
Vol 398 (5-6) ◽  
pp. 589-606 ◽  
Author(s):  
Veena Nambiar Potheraveedu ◽  
Miriam Schöpel ◽  
Raphael Stoll ◽  
Rolf Heumann
Keyword(s):  
Neuronal Degeneration ◽  
Amino Acid Uptake ◽  
Early Response ◽  
Small Gtpase ◽  
Cellular Aging ◽  
Synaptic Activity ◽  
Cellular Growth ◽  
Mammalian Brain ◽  
Acid Uptake ◽  
And Function

AbstractThe small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb’s activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake. The subcellular localization of Rheb and its interacting proteins critically regulate its activity and function. In stem cells, constitutive activation of Rheb enhances differentiation at the expense of self-renewal partially explaining the adverse effects of deregulated Rheb in the mammalian brain. In the context of various cellular stress conditions such as oxidative stress, ER-stress, death factor signaling, and cellular aging, Rheb activation surprisingly enhances rather than prevents cellular degeneration. This review addresses cell type- and cell state-specific function(s) of Rheb and mainly focuses on neurons and their surrounding glial cells. Mechanisms will be discussed in the context of therapy that interferes with Rheb’s activity using the antibiotic rapamycin or low molecular weight compounds.

scholarly journals Molecular mechanism of Aspergillus fumigatus biofilm disruption by fungal and bacterial glycoside hydrolases

2019 ◽  
Vol 294 (28) ◽  
pp. 10760-10772 ◽  
Author(s):  
François Le Mauff ◽  
Natalie C. Bamford ◽  
Noor Alnabelseya ◽  
Yongzhen Zhang ◽  
Perrin Baker ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Glycoside Hydrolase ◽  
Molecular Mechanisms ◽  
Glycoside Hydrolases ◽  
Structure Alignment ◽  
Glycoside Hydrolase Family ◽  
Fungal Virulence ◽  
Multifunctional Protein ◽  
Polysaccharide Biosynthesis ◽  
And Function

During infection, the fungal pathogen Aspergillus fumigatus forms biofilms that enhance its resistance to antimicrobials and host defenses. An integral component of the biofilm matrix is galactosaminogalactan (GAG), a cationic polymer of α-1,4-linked galactose and partially deacetylated N-acetylgalactosamine (GalNAc). Recent studies have shown that recombinant hydrolase domains from Sph3, an A. fumigatus glycoside hydrolase involved in GAG synthesis, and PelA, a multifunctional protein from Pseudomonas aeruginosa involved in Pel polysaccharide biosynthesis, can degrade GAG, disrupt A. fumigatus biofilms, and attenuate fungal virulence in a mouse model of invasive aspergillosis. The molecular mechanisms by which these enzymes disrupt biofilms have not been defined. We hypothesized that the hydrolase domains of Sph3 and PelA (Sph3h and PelAh, respectively) share structural and functional similarities given their ability to degrade GAG and disrupt A. fumigatus biofilms. MALDI-TOF enzymatic fingerprinting and NMR experiments revealed that both proteins are retaining endo-α-1,4-N-acetylgalactosaminidases with a minimal substrate size of seven residues. The crystal structure of PelAh was solved to 1.54 Å and structure alignment to Sph3h revealed that the enzymes share similar catalytic site residues. However, differences in the substrate-binding clefts result in distinct enzyme-substrate interactions. PelAh hydrolyzed partially deacetylated substrates better than Sph3h, a finding that agrees well with PelAh's highly electronegative binding cleft versus the neutral surface present in Sph3h. Our insight into PelAh's structure and function necessitate the creation of a new glycoside hydrolase family, GH166, whose structural and mechanistic features, along with those of GH135 (Sph3), are reported here.

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