PTEN and Autism With Macrocepaly

2013 ◽  
Author(s):  
Craig M. Powell
Keyword(s):  
Tumor Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Clinical Phenotype ◽  
Model Systems ◽  
Tumor Cell Lines ◽  
Gene Encoding ◽  
Increased Risk ◽  
The Brain

Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN) is a gene encoding an intracellular signaling molecule. PTEN was originally discovered as the gene responsible for a subset of familial hamartoma (tumor) syndromes associated with increased risk for certain cancers (Nelen et al., 1997) and as a gene often mutated in human cancers and tumor cell lines (Li et al., 1997; Steck et al., 1997). More recently, mutations in PTEN have been linked genetically to the clinical phenotype of autism or developmental delay with macrocephaly (Boccone et al., 2006; Butler et al., 2005; Buxbaum et al., 2007; Goffin, Hoefsloot, Bosgoed, Swillen, & Fryns, 2001; Herman, Butter, et al., 2007; McBride et al., 2010; Orrico et al., 2009; Stein, Elias, Saenz, Pickler, & Reynolds, 2010; Varga, Pastore, Prior, Herman, & McBride, 2009; Zori, Marsh, Graham, Marliss, & Eng, 1998). This chapter examines the role of PTEN in intracellular signaling, the link between PTEN signaling pathways and other autism-related genes and signaling pathways, the genetic relationship between PTEN and autism, model systems in which effects of Pten deletion on the brain have been studied, and promising preclinical data identifying therapeutic targets for patients with autism/macrocephaly associated with PTEN mutations.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals Association between Risk Factors for Vascular Dementia and Adiponectin

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Juhyun Song ◽  
Won Taek Lee ◽  
Kyung Ah Park ◽  
Jong Eun Lee
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Signal Transduction ◽  
Vascular Dementia ◽  
Case Control ◽  
Case Control Studies ◽  
Insulin Signal Transduction ◽  
Increased Risk ◽  
The Brain

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

Abstract B113: Role of I‐TAC‐binding receptors CXCR3 and CXCR7 in biology of various tumor cell lines

2009 ◽  
Author(s):  
Katarzyna Miekus ◽  
Danuta Jarocha ◽  
Elzbieta Trzyna ◽  
Marcin Majka
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines

scholarly journals Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function

2019 ◽  
Vol 4 (2) ◽  
pp. 90-92 ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Quan Jiang ◽  
Zhenggang Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Brain Parenchyma ◽  
Glymphatic System ◽  
Impaired Cognitive Function ◽  
Increased Risk ◽  
The Brain

Diabetes mellitus (DM) is a common metabolic disease in the middle-aged and older population, and is associated with cognitive impairment and an increased risk of developing dementia. The glymphatic system is a recently characterised brain-wide cerebrospinal fluid and interstitial fluid drainage pathway that enables the clearance of interstitial metabolic waste from the brain parenchyma. Emerging data suggest that DM and ageing impair the glymphatic system, leading to accumulation of metabolic wastes including amyloid-β within the brain parenchyma, and consequently provoking cognitive dysfunction. In this review, we concisely discuss recent findings regarding the role of the glymphatic system in DM and ageing associated cognitive impairment.

scholarly journals NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 692
Author(s):  
Erika Mikulenkova ◽  
Jakub Neradil ◽  
Ondrej Vymazal ◽  
Jan Skoda ◽  
Renata Veselska
Keyword(s):  
Tumor Cell ◽  
Nuclear Localization ◽  
Cell Types ◽  
Distal Region ◽  
Cell Fractionation ◽  
Tumor Cell Lines ◽  
Double Immunofluorescence ◽  
Transcriptional Regulatory ◽  
Mother Centriole

NANOG is a transcription factor involved in the regulation of pluripotency and stemness. The functional paralog of NANOG, NANOGP8, differs from NANOG in only three amino acids and exhibits similar reprogramming activity. Given the transcriptional regulatory role played by NANOG, the nuclear localization of NANOG/NANOGP8 has primarily been considered to date. In this study, we investigated the intriguing extranuclear localization of NANOG and demonstrated that a substantial pool of NANOG/NANOGP8 is localized at the centrosome. Using double immunofluorescence, the colocalization of NANOG protein with pericentrin was identified by two independent anti-NANOG antibodies among 11 tumor and non-tumor cell lines. The validity of these observations was confirmed by transient expression of GFP-tagged NANOG, which also colocalized with pericentrin. Mass spectrometry of the anti-NANOG immunoprecipitated samples verified the antibody specificity and revealed the expression of both NANOG and NANOGP8, which was further confirmed by real-time PCR. Using cell fractionation, we show that a considerable amount of NANOG protein is present in the cytoplasm of RD and NTERA-2 cells. Importantly, cytoplasmic NANOG was unevenly distributed at the centrosome pair during the cell cycle and colocalized with the distal region of the mother centriole, and its presence was markedly associated with centriole maturation. Along with the finding that the centrosomal localization of NANOG/NANOGP8 was detected in various tumor and non-tumor cell types, these results provide the first evidence suggesting a common centrosome-specific role of NANOG.

scholarly journals The Role of Acrolein and NADPH Oxidase in the Granulocyte-Mediated Growth-Inhibition of Tumor Cells

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 292 ◽  
Author(s):  
Morana Jaganjac ◽  
Tanja Matijevic Glavan ◽  
Neven Zarkovic
Keyword(s):  
Nadph Oxidase ◽  
Tumor Cell ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Redox Homeostasis ◽  
Peroxidation Of Lipids ◽  
Tlr4 Expression ◽  
Antitumor Effects ◽  
Reactive Aldehydes

: Although granulocytes are the most abundant leukocytes in human blood, their involvement in the immune response against cancer is not well understood. While granulocytes are known for their “oxidative burst” when challenged with tumor cells, it is less known that oxygen-dependent killing of tumor cells by granulocytes includes peroxidation of lipids in tumor cell membranes, yielding formation of reactive aldehydes like 4-hydroxynonenal (4-HNE) and acrolein. In the present work, we investigate the role of reactive aldehydes on cellular redox homeostasis and surface toll-like receptor 4 (TLR4) expression. We have further study the granulocyte-tumor cell intercellular redox signaling pathways. The data obtained show that granulocytes in the presence of 4-HNE and acrolein induce excessive ROS formation in tumor cells. Acrolein was also shown to induce granulocyte TLR4 expression. Furthermore, granulocyte-mediated antitumor effects were shown to be mediated via HOCl intracellular pathway by the action of NADPH oxidase. However, further studies are needed to understand interaction between TLR4 and granulocyte-tumor cell intercellular signaling pathways.

scholarly journals Pathological processes and therapeutic advances in radioiodide refractory thyroid cancer

2017 ◽  
Vol 59 (4) ◽  
pp. R141-R154 ◽  
Author(s):  
Marika H Tesselaar ◽  
Johannes W Smit ◽  
James Nagarajah ◽  
Romana T Netea-Maier ◽  
Theo S Plantinga
Keyword(s):  
Thyroid Cancer ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Medullary Thyroid Cancer ◽  
Disease Remission ◽  
Intracellular Signaling Pathways ◽  
Oncogenic Mutations ◽  
Diagnostics And Therapy ◽  
Disease Present

While in most patients with non-medullary thyroid cancer (TC), disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations inBRAF,TERTpromoter andTP53are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated. Also immune, metabolic, stemness and microRNA pathways have emerged as important determinants of TC dedifferentiation and RAI resistance. These signaling pathways have major clinical implications since their targeting could inhibit TC progression and could enable redifferentiation to restore RAI sensitivity. In this review, we discuss the current insights into the pathological processes conferring dedifferentiation and RAI resistance in TC and elaborate on novel advances in diagnostics and therapy to improve the clinical outcome of RAI-refractory TC patients.

scholarly journals A thorny pathway of macrophage activating factor (GcMAF): from bench to bedside

2019 ◽  
Vol 23 (5) ◽  
pp. 624-631 ◽  
Author(s):  
A. A. Ostanin ◽  
S. S. Kirikovich ◽  
E. V. Dolgova ◽  
А. S. Proskurina ◽  
E. R. Chernykh ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Current Data ◽  
Antitumor Drug ◽  
Main Role ◽  
Gene Encoding ◽  
Surface Receptors ◽  
Increased Risk ◽  
Elevated Expression ◽  
Anti Tumor Activity

Vitamin D3 Binding Protein (DBP) is a multifunctional glycoprotein whose main role is to transport vitamin D3 and its metabolites, but it also is the precursor of the macrophage activating factor (GcMAF). DBP is converted to GcMAF as a result of site-specific selective deglycosylation under the action of β-galactosidase and sialidase, localized on activated B and T cells, respectively. GcMAF exerts its biological activity primarily as the capability of activating macrophages by enhancing their phagocytic function and producing ROS. Activation results in elevated expression of the specific macrophageal surface receptors involved in the recognition of tumor-associated antigens, as well as in the implementation of direct anticancer activity by inducing the apoptosis or necrosis of tumor cells. Increased interest in GcMAF is associated with its potential to be used in the clinic as a new antitumor drug. Besides its anti-tumor activity, GcMAF exerts a potential against a number of viral and neurodegenerative diseases associated with increased activity of N-acetylgalactosaminidase (nagalase) in the blood serum of patients. Nagalase is an enzyme that completely (rather than selectively) deglycosylates DBP so it cannot be converted to GcMAF, leading to immunodeficiency. Circulating DBP is composed of unmodified and O-glycosylated molecules with the glycosylation degree being dependent on the allelic variants of the gene encoding DBP. The role of DBP in the resistance of organism against a number of diseases is supported by the increased risk of a variety of severe illnesses (amyotrophic lateral sclerosis, colorectal cancer etc.) in patients deficient for GcMAF due to homozygosity for defective DBP alleles. In this review, we also will examine in detail the current data i) on the structure and functions of DBP, as the main precursor of GcMAF, ii) on the main mechanisms of GcMAF anticancer effect, iii) on the tumor strategy for neutralizing GcMAF activity, iv) on the results of GcMAF clinical trials in various cancers; and will discuss the available controversies regarding the positioning of GcMAF as an effective antitumor drug. 

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