1,721,028 research outputs found
Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: Focus on heteroreceptor complexes and related functional neurotrophic effects
No full textNeuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe heteroreceptor complexes between GPCR and RTKs in the central nervous system (CNS) and their functional effects in controlling a variety of neuronal effects, ranging from development, proliferation, differentiation and migration, to survival, repair, synaptic transmission and plasticity. In this interaction, RTKs can also recruit components of the G protein signaling cascade, creating a bidirectional intricate interplay that provides complex control over multiple cellular events. These heteroreceptor complexes, by the integration of different signals, have recently attracted a growing interest as novel molecular target for depressive disorders
Role of Bioactive Molecules on Neuroprotection, Oxidative Stress, and Neuroinflammation Modulation
Full text linkAs the global population ages, the burden of neurodegenerative and neurological disorders is dramatically increasing [...
An upstream enhancer and MEF2 transcription factors fine-tune the regulation of the Bdnf gene in cortical and hippocampal neurons
Full text link: The myocyte enhancer factor (MEF2) family of transcription factors, originally discovered for its pivotal role in muscle development and function, has emerged as an essential regulator in various aspects of brain development and neuronal plasticity. The MEF2 transcription factors are known to regulate numerous important genes in the nervous system, including brain-derived neurotrophic factor (BDNF), a small secreted neurotrophin responsible for promoting the survival, growth, and differentiation of neurons. The expression of the Bdnf gene is spatiotemporally controlled by various transcription factors binding to both its proximal and distal regulatory regions. While previous studies have investigated the connection between MEF2 transcription factors and Bdnf, the endogenous function of MEF2 factors in the transcriptional regulation of Bdnf remains largely unknown. Here, we aimed to deepen the knowledge of MEF2 transcription factors and their role in the regulation of Bdnf comparatively in rat cortical and hippocampal neurons. As a result, we demonstrate that the MEF2 transcription factor-dependent enhancer located at -4.8 kb from the Bdnf gene regulates the endogenous expression of Bdnf in hippocampal neurons. In addition, we confirm neuronal-activity dependent activation of the -4.8 kb enhancer in vivo. Finally, we show that specific MEF2 family transcription factors have unique roles in regulation of Bdnf, with the specific function varying based on the particular brain region and stimuli. Altogether, we present MEF2 family transcription factors as crucial regulators of Bdnf expression, finetuning Bdnf expression through both distal and proximal regulatory regions
Manipulation of HSP70-SOD1 Expression Modulates SH-SY5Y Differentiation and Susceptibility to Oxidative Stress-Dependent Cell Damage: Involvement in Oxotremorine-M-Mediated Neuroprotective Effects
Full text linkThe differentiation of neural progenitors is a complex process that integrates different signals to drive transcriptional changes, which mediate metabolic, electrophysiological, and morphological cellular specializations. Understanding these adjustments is essential within the framework of stem cell and cancer research and therapy. Human neuroblastoma SH-SY5Y cells, widely used in neurobiology research, can be differentiated into neuronal-like cells through serum deprivation and retinoic acid (RA) supplementation. In our study, we observed that the differentiation process triggers the expression of Heat Shock Protein 70 (HSP70). Notably, inhibition of HSP70 expression by KNK437 causes a dramatic increase in cell death. While undifferentiated SH-SY5Y cells show a dose-dependent decrease in cell survival following exposure to hydrogen peroxide (H2O2), differentiated cells become resistant to H2O2-induced cell death. Interestingly, the differentiation process enhances the expression of SOD1 protein, and inhibition of HSP70 expression counteracts this effect and increases the susceptibility of differentiated cells to H2O2-induced cell death, suggesting that the cascade HSP70-SOD1 is involved in promoting survival against oxidative stress-dependent damage. Treatment of differentiated SH-SY5Y cells with Oxotremorine-M (Oxo), a muscarinic acetylcholine receptor agonist, enhances the expression of HSP70 and SOD1 and counteracts tert–Butyl hydroperoxide-induced cell death and reactive oxygen species (ROS) generation. It is worth noting that co-treatment with KNK437 reduces SOD1 expression and Oxo-induced protection against oxidative stress damage, suggesting the involvement of HSP70/SOD1 signaling in this beneficial effect. In conclusion, our findings demonstrate that manipulation of the HSP70 signal modulates SH-SY5Y differentiation and susceptibility to oxidative stress-dependent cell death and unravels novel mechanisms involved in Oxo neuroprotective functions. Altogether these data provide novel insights into the mechanisms underlying neuronal differentiation and preservation under stress conditions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
PROTEOMIC CHANGES INDUCED BY LOW-INTENSITY ENDURANCE EXERCISE IN MDX MOUSE QUADRICEPS: CORRELATION WITH REDUCTION OF MUSCLE DEGENERATION.
No full textPrevious study showed that low-intensity endurance exercise induced a significant recovery of damaged skeletal muscle in mdx mice, probably by reducing the degeneration of dystrophic muscle1. In order to explore the molecular basis of this observation, we perfomed a proteomic analysis to evaluate changes in proteins profiling of quadriceps dystrophic muscles of exercised versus sedentary mdx mice. Four protein spots were found significantly changed and were identified as three isoforms of Carbonic anhydrase 3 (CA3) and as superoxide dismutase [Cu-Zn] (SODC). Protein levels of CA3 isoforms were found significantly up-regulated in quadriceps of sedentary mdx mice (MDX-Sed) and were completely restored to wild type values in quadriceps of exercised mdx mice (MDX-Ex). Protein levels of SODC were found down-regulated in quadriceps of sedentary mdx mice and were significantly restored to wild type values in quadriceps of exercised mdx mice. These proteomic data, validated by Western blot analysis, indicate that low-intensity endurance exercise, by modulating some proteins involved in oxidative stress defense, may in part contribute to reduce the reported cell degeneration in mdx muscles1.
Further investigations are needed to better define the extension of proteins change in MDX-Ex versus MDX-Sed mice and its correlation with the recovery of damaged fibers in MDX-Ex mice
Current disease modifying approaches to treat Parkinson's disease
Full text linkParkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candidates to counteract and possibly halt cell degeneration in PD. In particular, studies employing glial cell line-derived neurotrophic factor (GDNF) and its family member neurturin (NRTN), as well as the recently described cerebral dopamine neurotrophic factor (CDNF) and the mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown positive results in protecting and repairing dopaminergic neurons in various models of PD. Other substances with trophic actions in dopaminergic neurons include neuropeptides and small compounds that target different pathways impaired in PD, such as increased cell stress, protein handling defects, dysfunctional mitochondria and neuroinflammation. In this review, we will highlight the recent developments in this field with a focus on trophic factors and substances having the potential to beneficially influence the viability and functions of dopaminergic neurons as shown in preclinical or in animal models of PD.Peer reviewe
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