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P53 & neurobiology

Minhan Ka, Woo-Yang Kim
Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons...
March 2018: Neurobiology of Disease
Massimiliano Agostini, Gerry Melino, Francesca Bernassola
SIGNIFICANCE: The p53 family of transcription factors, including p53, p63, and p73, plays key roles in both biological and pathological processes, including cancer and neural development. Recent Advances: In recent years, a growing body of evidence has indicated that the entire p53 family is involved in the regulation of the central nervous system (CNS) functions as well as in the pathogenesis of several neurological disorders. Mechanistically, the p53 proteins control neuronal cell fate, terminal differentiation, and survival, via a complex interplay among the family members...
November 27, 2017: Antioxidants & Redox Signaling
Arpiné Ardzivian Elnar, Frédéric Desor, Fabian Marin, Rachid Soulimani, Christophe Nemos
Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10 ng/kg ∑6 NDL-PCBs). Our results revealed changes in the expression of 16658 genes in the neurons of the exposed mice...
February 3, 2015: Toxicology
Daiane Engel, Andréa D E Zomkowski, Vicente Lieberknecht, Ana Lúcia Rodrigues, Nelson H Gabilan
Structural alterations in the limbic system, neuronal cell loss, and low levels of neurotrophins have been implicated in the pathogenesis of depression. While it is generally accepted that increasing monoamine levels in the brain can effectively alleviate depression, the precise neurobiological mechanisms involved are unclear. In the present study, we examined the effects of two antidepressants, duloxetine and mirtazapine, on the expression of apoptotic and neurotrophic proteins in the cerebral cortex and hippocampus of mice...
June 2013: Journal of Psychiatric Research
Francesca Grespi, Gerry Melino
P73 is a member of the p53 transcription factors family with a prominent role in neurobiology, affecting brain development as well as controlling neuronal survival. Accordingly, p73 has been identified as key player in many age-related neurodegenerative diseases, such as Alzheimer's disease, neuroAIDS and Niemann-Pick type C disease. Here we investigate possible correlations of p73 with Parkinson disease. Tyrosine hydroxylase is a crucial player in Parkinson disease being the enzyme necessary for dopamine synthesis...
December 2012: Aging
Simone Di Giovanni, Khizr Rathore
The tumor suppressor p53 is a multifunctional sensor of a number of cellular signals and pathways essential for cell biology, including DNA damage, cell cycle regulation, apoptosis, angiogenesis and cell metabolism. In the last few years, a novel role for p53 in neurobiology has emerged, which includes a role in the regulation of neurite outgrowth and axonal regeneration. p53 integrates a number of extracellular signals that involve neurotrophins and axon guidance cues to modulate the cytoskeletal response associated with neurite outgrowth at both the transcriptional and post-translational level...
July 2012: Cell and Tissue Research
Richard Killick, Maria Niklison-Chirou, Richard Tomasini, Daniele Bano, Alessandro Rufini, Francesca Grespi, Tania Velletri, Paola Tucci, Berna S Sayan, Franco Conforti, Ewen Gallagher, Pierluigi Nicotera, Tak W Mak, Gerry Melino, Richard A Knight, Massimiliano Agostini
p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role...
April 2011: Molecular Neurobiology
Uwe Strähle, Clemens Grabher
Although first used experimentally for the genetic analysis of vertebrate development and neurobiology, the zebrafish has been adapted as a model for many human diseases. In recent years, the zebrafish embryo has increasingly attracted the attention of chemists and pharmacologists for its utility in identifying chemicals with pharmacological activity in a whole-animal context. Its experimental virtues make it an ideal system with which to identify new bioactive molecules, and to assess their toxicity and teratogenicity at medium-to-high throughput...
November 2010: Disease Models & Mechanisms
G Chazot, I V Gogoleva, O A Gromova, N M Ullubiev, A A Nikonov
In addition to well-documented mood-stabilizing effects, lithium can be used in the treatment of acute brain injuries (ischemia) and chronic (neurodegenerative) diseases. Recent in vitro and in vivo studies reveal that the long-term treatment with lithium up-regulates cell survival molecules (Bcl-2, cAMP-responsive element binding protein, GRP 78, brain-derived neurotrophic factor, Hsp70) and down-regulates pro-apoptotic activities (e.g., excitotoxicity, p53, Bax, caspase, cytochrome C release, beta-amyloid peptide production and tau hyperphosphorylation) thus preventing or even reversing the neuronal cell death and neurogenesis retardation...
2008: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Freda D Miller, David R Kaplan
One of the fundamental questions in neurobiology is how mammalian neurons survive for an organism's lifetime in the face of normal ongoing "wear and tear" that, in the case of neurons in the peripheral nervous system, even includes physical damage. Elucidating the mechanisms that control neuronal survival is of importance not only for our understanding of normal development of neuronal circuitry, but also to devise treatments for pathological situations such as traumatic injury, or neurodegenerative conditions...
February 1, 2007: Cell Cycle
Matthias Preusser, Christine Haberler, Johannes A Hainfellner
Malignant gliomas may manifest at any age including congenital and childhood cases. Peak incidence is, however, in adults older than 40 years. Males are more frequently affected than females. The sole unequivocal risk factor is therapeutic ionizing irradiation. Malignant gliomas comprise a spectrum of different tumor subtypes. Within this spectrum, glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma share as basic features preferential location in cerebral hemispheres, diffuse infiltration of brain tissue, fast tumor growth with fatal outcome within months or years...
June 2006: Wiener Medizinische Wochenschrift
Cristina Pelizon
A report on the British Society for Cell Biology (BSCB) meeting on 'Cell Biology and Neurobiology: A Meeting for Martin Raff', London, UK, 3-5 July 2002.
August 27, 2002: Genome Biology
Yuan Zhu, Luis F Parada
There are no effective therapies for many tumours of the nervous system. This is, in part, a consequence of their location within relatively inaccessible tissues. It is also likely, however, that the unique characteristics of the cells that give rise to these tumours create a set of conditions that facilitate tumour development. Here, we consider recent advances in molecular genetics, the development of mouse models and developmental neurobiology as they relate to tumours of neuroectodermal origin. It is likely that these advances will provide insight into underlying mechanisms and provide a rational framework for the development of effective interventions...
August 2002: Nature Reviews. Cancer
M F Lavin, P Concannon, R A Gatti
ATW8 was a unique opportunity to review the complex and growing field of ataxia-telangiectasia (A-T) research and to cross-fertilize ideas for new experimental designs. A-T biology now encompasses human and mouse neurology, neurobiology, immunology, radiobiology, cell signalling, cell cycle checkpoints, gametogenesis, and oncogenesis, as well as radiotherapy, cancer epidemiology, premature aging, cytogenetics, and DNA repair mechanisms. By an as yet undetermined mechanism, the ATM protein appears to sense double strand breaks (DSB) during meiosis or mitosis, or breaks consequent to the damage of free radicals which are generated during the metabolism of food...
August 1, 1999: Cancer Research
K B Andersson, B S Skålhegg
Genetic modification of mice by homologous recombination has rapidly become a central tool within molecular medicine and molecular biology. The use of such techniques allows precise mutation of single genes and study of the direct consequences in intact animals. A decade has passed since the a series of landmark studies demonstrated the feasibility of genetically modifying embryonic stem cells in mice by homologous recombination. This initiated the whole field of gene targeting, or "knockout" technology in mice...
October 20, 1998: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
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