scholarly journals Synaptic Wnt/GSK3βSignaling Hub in Autism

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mario O. Caracci ◽  
Miguel E. Ávila ◽  
Giancarlo V. De Ferrari
Keyword(s):  
De Novo ◽  
Glycogen Synthase ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Glycogen Synthase Kinase 3 ◽  
Basic Information ◽  
The Central Nervous System ◽  
Spectrum Disorders ◽  
Cell Signaling Pathways

Hundreds of genes have been associated with autism spectrum disorders (ASDs) and the interaction of weak andde novovariants derive from distinct autistic phenotypes thus making up the “spectrum.” The convergence of these variants in networks of genes associated with synaptic function warrants the study of cell signaling pathways involved in the regulation of the synapse. The Wnt/β-catenin signaling pathway plays a central role in the development and regulation of the central nervous system and several genes belonging to the cascade have been genetically associated with ASDs. In the present paper, we review basic information regarding the role of Wnt/β-catenin signaling in excitatory/inhibitory balance (E/I balance) through the regulation of pre- and postsynaptic compartments. Furthermore, we integrate information supporting the role of the glycogen synthase kinase 3β(GSK3β) in the onset/development of ASDs through direct modulation of Wnt/β-catenin signaling. Finally, given GSK3βactivity as key modulator of synaptic plasticity, we explore the potential of this kinase as a therapeutic target for ASD.

scholarly journals The Role of the FOXP Family of Transcription Factors in ASD

2012 ◽  
Vol 33 (5) ◽  
pp. 251-260 ◽  
Author(s):  
J. Michael Bowers ◽  
Genevieve Konopka
Keyword(s):  
Transcription Factors ◽  
Animal Behavior ◽  
Autism Spectrum ◽  
Evolution Of Language ◽  
Complex Genetics ◽  
Neurodevelopmental Disease ◽  
Key Players ◽  
The Central Nervous System ◽  
Spectrum Disorders

Autism spectrum disorders (ASD) is a neurodevelopmental disease with complex genetics; however, the genes that are responsible for this disease still remain mostly unknown. Here, we focus on the FOXP family of transcription factors as there is emerging evidence strongly linking these genes to ASD and other genes implicated in ASD. The FOXP family of genes includes three genes expressed in the central nervous system: FOXP1, FOPX2, and FOXP4. This unique group of transcription factors has known functions in brain development as well as the evolution of language. We will also discuss the other genes including transcriptional targets of FOXP genes that have been found to be associated with language and may be important in the pathophysiology of ASD. Finally, we will review the emerging animal models currently being used to study the function of the FOXP genes within the context of ASD symptomology. The combination of gene expression and animal behavior is critical for elucidating how genes such as the FOXP family members are key players within the framework of the developing brain.

scholarly journals An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 216 ◽  
Author(s):  
Marika Cordaro ◽  
Salvatore Cuzzocrea ◽  
Rosalia Crupi
Keyword(s):  
Nervous System ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Monocytes And Macrophages ◽  
Central Nervous Systems ◽  
The Central Nervous System ◽  
Spectrum Disorders ◽  
Dynamic Series ◽  
Preclinical And Clinical Studies

The inflammation process represents of a dynamic series of phenomena that manifest themselves with an intense vascular reaction. Neuroinflammation is a reply from the central nervous system (CNS) and the peripheral nervous system (PNS) to a changed homeostasis. There are two cell systems that mediate this process: the glia of the CNS and the lymphocites, monocytes, and macrophages of the hematopoietic system. In both the peripheral and central nervous systems, neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, and in neuropsychiatric illnesses, such as depression and autism spectrum disorders. The resolution of neuroinflammation is a process that allows for inflamed tissues to return to homeostasis. In this process the important players are represented by lipid mediators. Among the naturally occurring lipid signaling molecules, a prominent role is played by the N-acylethanolamines, namely N-arachidonoylethanolamine and its congener N-palmitoylethanolamine, which is also named palmitoylethanolamide or PEA. PEA possesses a powerful neuroprotective and anti-inflammatory power but has no antioxidant effects per se. For this reason, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treating neuroinflammation. The aim of this review is to discuss the role of ultramicronized PEA and co-ultramicronized PEA with luteolin in several neurological diseases using preclinical and clinical approaches.

scholarly journals Glycogen Synthase Kinase-3 Is Required for EfficientDictyosteliumChemotaxis

2010 ◽  
Vol 21 (15) ◽  
pp. 2788-2796 ◽  
Author(s):  
Regina Teo ◽  
Kimberley J. Lewis ◽  
Josephine E. Forde ◽  
W. Jonathan Ryves ◽  
Jonathan V. Reddy ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Glycogen Synthase ◽  
Cell Aggregation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cell Fate Determination ◽  
Cell Signaling Pathways

Glycogen synthase kinase-3 (GSK3) is a highly conserved protein kinase that is involved in several important cell signaling pathways and is associated with a range of medical conditions. Previous studies indicated a major role of the Dictyostelium homologue of GSK3 (gskA) in cell fate determination during morphogenesis of the fruiting body; however, transcriptomic and proteomic studies have suggested that GSK3 regulates gene expression much earlier during Dictyostelium development. To investigate a potential earlier role of GskA, we examined the effects of loss of gskA on cell aggregation. We find that cells lacking gskA exhibit poor chemotaxis toward cAMP and folate. Mutants fail to activate two important regulatory signaling pathways, mediated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and target of rapamycin complex 2 (TORC2), which in combination are required for chemotaxis and cAMP signaling. These results indicate that GskA is required during early stages of Dictyostelium development, in which it is necessary for both chemotaxis and cell signaling.

scholarly journals Exploring the Association of Autism Spectrum Disorders and Constipation through Analysis of the Gut Microbiome

2021 ◽  
Vol 18 (2) ◽  
pp. 667
Author(s):  
Shih-Chen Fu ◽  
Chung-Han Lee ◽  
Hsiuying Wang
Keyword(s):  
Autism Spectrum Disorders ◽  
Gut Microbiome ◽  
Gastrointestinal Symptoms ◽  
Autism Spectrum ◽  
Published Data ◽  
Microbial Composition ◽  
The Central Nervous System ◽  
Spectrum Disorders ◽  
Key Aspects

Over the past two decades, research into the role of the gut microbiome in regulating the central nervous system has rapidly increased. Several neurodevelopmental diseases have been linked to the unbalance of gut microbiota, including autism. Children on the autism spectrum often suffer from gastrointestinal symptoms, including constipation, which is four times more prevalent than it is in children without autism spectrum disorders (ASD). Although studies in animals have shown the crucial role of the microbiota in key aspects of neurodevelopment, there is currently no consensus on how the alteration of microbial composition affects the pathogenesis of ASD, let alone how it exerts an impact on the following comorbidities. In our study, we were able to control the effects of constipation on gut dysbiosis and distinguish neuropathological-related and gastrointestinal-related bacteria in ASD patients separately. By analyzing published data, eight additional bacteria significantly altered in autistic individuals were identified in our study. All of them had a decreased relative abundance in ASD patients, except Lactobacillaceae and Peptostreptococcaceae. Eighteen and eleven bacteria were significantly correlated with ASD symptoms and constipation, respectively. Among those, six bacteria were overlapped between the groups. We have found another six bacteria highly associated with constipation status in ASD patients only. By conducting Welch’s t-test, we were able to demonstrate the critical roles of microbes in ASD core and gastrointestinal symptoms and raised the hypotheses of their confounding and mediating effects on the relationship between the two symptoms.

The role of de novo mutations in the genetics of autism spectrum disorders

2014 ◽  
Vol 15 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Michael Ronemus ◽  
Ivan Iossifov ◽  
Dan Levy ◽  
Michael Wigler
Keyword(s):  
Autism Spectrum Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Spectrum Disorders

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Chang-geng Song ◽  
Xin Kang ◽  
Fang Yang ◽  
Wan-qing Du ◽  
Jia-jia Zhang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
Interneuron Development

Abstract In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

Critical role of dysfunctional mitochondria and defective mitophagy in autism spectrum disorders

2021 ◽  
Vol 168 ◽  
pp. 138-145
Author(s):  
Yuan-Mei Wang ◽  
Ming-Yue Qiu ◽  
Qing Liu ◽  
Huang Tang ◽  
Hong-Feng Gu
Keyword(s):  
Autism Spectrum Disorders ◽  
Critical Role ◽  
Autism Spectrum ◽  
Spectrum Disorders
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