Download or read book Characterization of Neuronal Protein Complexes to Identify Molecular Underpinnings of Autism Spectrum Disorder written by Zhuoran Wu and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autism spectrum disorder (ASD), a complex neurodevelopmental disorder that affects brain development, social and communication skills in children and adults, poses a tremendous burden on caregivers and the healthcare system. Although advances in genetics has enabled the discovery of hundreds of ASD-associated genes, the biological context of how these ASD-linked risk genes contribute to the pathophysiology of the disorder remains unclear. The study of protein-protein interactions (PPI) offers a valuable framework for elucidating this biological context, so far only few human proteomics studies were targeted to ASD. Many cell-context-dependent human ASD interactions involved in neuronal processes are unknown. This study addresses this gap by systematically. Fourty six literature-validated ASD-linked proteins expressed in differentiated SH-SY5Y cells were studied using immunoprecipitation coupled with mass spectrometry (IP/MS) to generate a high-quality PPI network, outlining the organization of individual co-purified proteins in multiprotein complexes. Enrichment analysis confirmed the disease relevance of the PPI network and revealed significant enrichment for genes involved in gene expression, cellular transport and mitochondrial (mt) processes. From the high-confidence PPI network, two previously unreported interacting protein pairs of interest (i.e. FMRP-TWNK and DYRK1A-TRMT61B) linking mitochondria with ASD were selected for further characterization. Co-purifying proteins were validated experimentally by co-immunoprecipitation. Knockouts of the interacting protein pairs of interest were generated, with knockout efficacy confirmed by immunoblotting. The interaction between the ASD-linked fragile X mental retardation protein (FMRP) and the mt twinkle DNA helicase (TWNK) were found to play a role in maintaining mtDNA integrity. As well, a functional role between the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK1A) and the mt tRNA methyltransferase 61B (TRMT61B) in tRNA methylation were established. While additional work is needed to dissect the molecular mechanisms of these interactions, the findings from this study offers support to the validity of the molecular models that were proposed. In conclusion, through this Master's thesis, I was able to demonstrate that the ASD-linked PPI network generated by IP/MS can offer a powerful means for discovering new ASD links and providing future directions for understanding the role of mt in ASD biology.

Download or read book Autism Spectrum Disorder New Insights Into Molecular Pathophysiology and Therapeutic Development written by Junyu Xu and published by Frontiers Media SA. This book was released on 2020-09-18 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Download or read book A Time for Metabolism and Hormones written by Paolo Sassone-Corsi and published by Springer. This book was released on 2016-04-04 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent years have seen spectacular advances in the field of circadian biology. These have attracted the interest of researchers in many fields, including endocrinology, neurosciences, cancer, and behavior. By integrating a circadian view within the fields of endocrinology and metabolism, researchers will be able to reveal many, yet-unsuspected aspects of how organisms cope with changes in the environment and subsequent control of homeostasis. This field is opening new avenues in our understanding of metabolism and endocrinology. A panel of the most distinguished investigators in the field gathered together to discuss the present state and the future of the field. The editors trust that this volume will be of use to those colleagues who will be picking up the challenge to unravel how the circadian clock can be targeted for the future development of specific pharmacological strategies toward a number of pathologies.

Download or read book Functional Characterization of Altered Neurodevelopmental Mechanisms in Autism Using Patient Specific Induced Pluripotent Stem Cells written by Brooke A DeRosa and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: To date, numerous candidate genes have been associated with autism spectrum disorder (ASD) with many of these genes known to have important roles in synaptic function and the development of neural circuits. This suggests that certain neurobiological processes could be commonly altered in ASD. Therefore, although there is a great deal of clinical and genetic heterogeneity in ASDs, there may be convergent deficits in key molecular mechanisms which underlie the disease. Although this is encouraging, a lack of appropriate human-based models of complex neurodevelopmental disorders has greatly hindered investigations of convergent neurobiology in ASD. Patient-specific induced pluripotent stem cells (iPSCs) can be used to model brain region-specific neuronal development in genetic backgrounds known to result in certain pathological conditions. This ability to model neurodevelopment in vitro permits the characterization of disease mechanisms that manifest themselves during the early steps of brain development in ASD, facilitating the identification of common molecular mechanisms disrupted in this disorder. Importantly, the identification of common pathways in ASD that are disrupted in the early stages of disease development could serve as important candidate targets for therapeutic intervention. Patient-specific iPSC lines were derived from the whole blood of individuals affected with idiopathic ASD, and subsequently differentiated into cortical neurons for up to 135 days in culture. The findings of transcriptome and gene network analysis indicate that iPSC-derived neurons from our cohort of ASD individuals have altered expression of genes associated with synaptic function, Wnt signaling, neuronal differentiation, and various processes involving the extracellular matrix (i.e. axon guidance and cell migration). Furthermore, our data show that genes previously implicated in ASD and intellectual disability are significantly overrepresented in gene coexpression networks related to synaptic function that are transcriptionally co-regulated by Wnt. Finally, we demonstrate that neurons derived from our sample cohort of idiopathic ASD individuals have excessive neurite outgrowth at an early stage of cortical neurogenesis. In sum, our data indicate that convergent molecular disturbances in ASD impact synaptic development and function, metabolism, and cellular molecular interactions involving the extracellular matrix. Furthermore, our results from transcriptome and gene-network analysis both indicate considerable transcriptional dysregulation during earlier stages of neuronal development.

Download or read book The Molecular Mechanisms and Neuronal Consequences of PTEN Autism associated Mutations written by Catherine J. Fricano-Kugler and published by . This book was released on 2015 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: Phosphatase and Tensin Homologue (PTEN) is a phosphatase that negatively regulates the PI3K pathway by dephosphorylating phopsphatidylinositol (3,4,5)-triphphosphate to phosphatidylinositol (4,5)-bisphosphate. The PI3K pathway is important for the regulation of cell growth and proliferation. Various PTEN mutations have been discovered in children with Autism Spectrum Disorder (ASD) with macrocephaly. This thesis research aims to elucidate how these distinct specific point mutations in PTEN, found in various functional domains of the protein, each contributes to the loss of PTEN function thought to be central to these associated forms of ASD. This was accomplished by using replication deficient viruses to replace endgogenous PTEN in developing mouse hippocampal granule neurons with the ASD mutant forms and assessing neuronal morphology, or expressing these mutant forms in human cell lines to investigate their biochemical properties. Having characterized a wider array of mutations, we have identified a set of ASD-associated mutations, F241S, D252G, W274L, and N726S, that are nuclear excluded, loss-of-function, and unstable in neurons. Trafficking these proteins to the nucleus improved their PIP3 cataltyic function and their ability to rescue the loss-of-function phenotype with respect to neuronal hypertrophy. We have also assessed various molecular environmental factors that may exacerbate loss of PTEN function, and determined that circulating fatty acids increase this neuronal hypertrophy. Subsequently, we have performed exploratory immunoprecipitation/mass spectrometry analysis to identify protein-protein interactions that are affected by ASD-associated point mutations. Overall, this research identifies potential molecular mechanism by which ASD associated PTEN mutations lead to a loss of protein function and thus dysregulated neuronal form, and likely, function. Understanding the molecular consequences of PTEN loss of function is vital for enabling researchers to create novel therapies for ASD.

Download or read book Autism Spectrum Disorders written by Andreas M. Grabrucker and published by . This book was released on 2021 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autism spectrum disorders are developmental disorders. Individuals with autism spectrum disorders develop differently. These differences are usually present in social interaction, communication, and sensory processing, and become visible through a wide variety of behavioral responses that differ from individuals without autism spectrum disorders. Despite significant research efforts, the exact causes of autism spectrum disorders remain poorly understood; however, researchers have gained extensive insights into possible pathomechanisms, even at the molecular level of cells. Many diagnostic criteria have been developed, adapted, and improved. The eight chapters in this book highlight the current state-of-the-art in many areas of autism spectrum disorders. Chapter 1 provides an overview of the epidemiology of autism spectrum disorders and the current knowledge of the underlying pathogenic mechanisms. Chapter 2 summarizes the diagnostic criteria and procedures and highlights present and upcoming therapeutic strategies. Chapter 3 reviews the adverse events and trauma in people with autism spectrum disorders. Chapters 4 and 5 focus on atypical sensory processing, and Chapter 6 discusses the genetic overlap of autism spectrum disorders with other neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD), depression, and schizophrenia. Chapter 7 focuses on the contribution of abnormalities in mitochondria, and chapter 8 discusses gut-brain interactions and a potential role for microbiota in autism spectrum disorders. This book is aimed primarily at clinicians and scientists, but many areas will also be of interest to the layperson.

Download or read book Brain Connectivity in Autism written by Rajesh K. Kana and published by Frontiers E-books. This book was released on 2014-09-23 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain's ability to process information crucially relies on connectivity. Understanding how the brain processes complex information and how such abilities are disrupted in individuals with neuropsychological disorders will require an improved understanding of brain connectivity. Autism is an intriguingly complex neurodevelopmental disorder with multidimensional symptoms and cognitive characteristics. A biological origin for autism spectrum disorders (ASD) had been proposed even in the earliest published accounts (Kanner, 1943; Asperger, 1944). Despite decades of research, a focal neurobiological marker for autism has been elusive. Nevertheless, disruptions in interregional and functional and anatomical connectivity have been a hallmark of neural functioning in ASD. Theoretical accounts of connectivity perceive ASD as a cognitive and neurobiological disorder associated with altered functioning of integrative circuitry. Neuroimaging studies have reported disruptions in functional connectivity (synchronization of activated brain areas) during cognitive tasks and during task-free resting states. While these insights are valuable, they do not address the time-lagged causality and directionality of such correlations. Despite the general promise of the connectivity account of ASD, inconsistencies and methodological differences among studies call for more thorough investigations. A comprehensive neurological account of ASD should incorporate functional, effective, and anatomical connectivity measures and test the diagnostic utility of such measures. In addition, questions pertaining to how cognitive and behavioral intervention can target connection abnormalities in ASD should be addressed. This research topic of the Frontiers in Human Neuroscience addresses “Brain Connectivity in Autism” primarily from cognitive neuroscience and neuroimaging perspectives.

Download or read book Early Start Denver Model for Young Children with Autism written by Sally J. Rogers and published by Guilford Publications. This book was released on 2020-05-14 with total page 323 pages. Available in PDF, EPUB and Kindle. Book excerpt: From leading authorities, this state-of-the-art manual presents the Early Start Denver Model (ESDM), the first comprehensive, empirically tested intervention specifically designed for toddlers and preschoolers with autism spectrum disorder. Supported by the principles of developmental psychology and applied behavior analysis, ESDM’s intensive teaching interventions are delivered within play-based, relationship-focused routines. The manual provides structured, hands-on strategies for working with very young children in individual and group settings to promote development in such key domains as imitation; communication; social, cognitive, and motor skills; adaptive behavior; and play. Implementing individualized treatment plans for each child requires the use of an assessment tool, the Early Start Denver Model Curriculum Checklist for Young Children with Autism. A nonreproducible checklist is included in the manual for reference, along with instructions for use; 8½" x 11" checklists are sold separately in sets of 15 ready-to-use booklets. See also the authors' related parent guide, An Early Start for Your Child with Autism.

Download or read book Reviews on Biomarker Studies in Psychiatric and Neurodegenerative Disorders written by Paul C. Guest and published by Springer. This book was released on 2019-02-12 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book includes a series of reviews on general aspects of biomarker use in the study of psychiatric and neurodegenerative diseases and the development of medications involved in their treatment. It describes the pros and cons of the various approaches and covers the successes and failures in this research field. It is only by a thorough understanding of the shortcomings that progress can be made. The overall goal is to facilitate the understanding and treatment of these disorders, by providing a viable mechanism of catching up with other areas of modern medicine, such as diabetes and heart disease. Finally, it is anticipated that the development and application of valid biomarker tests and the leveraging of novel drug targets will help the fields of psychiatry on neurodegenerative disorders move into the area of personalized medicine where the right patients can receive the right medication at the right time for the best possible outcome.

Download or read book Autism Spectrum Disorders written by Stephen Deutsch and published by BoD – Books on Demand. This book was released on 2011-08-01 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estimated prevalence rates of autism spectrum disorders (ASDs) have increased at an alarming rate over the past decade; current estimates stand as high as 1 in 110 persons in the population with a higher ratio of affected males to females. In addition to their emotional impact on the affected persons and their family members (in fact, the latter are often unrecognized unaffected “patients” themselves), the economic and social impacts of ASDs on society are staggering. Persons with ASDs will need interdisciplinary approaches to complex treatment and life planning, including, but not limited to, special education, speech and language therapy, vocational skills training and rehabilitation, social skills training and cognitive remediation, in addition to pharmacotherapy. The current book highlights some of the recent research on nosology, etiology, and pathophysiology. Additionally, the book touches on the implications of new research for treatment and genetic counseling. Importantly, because the field is advancing rapidly, no book can be considered the final word or finished product; thus, the availability of open access rapid publication is a mechanism that will help to assure that readers remain current and up-to-date.

Download or read book Comprehensive Guide to Autism written by Vinood B. Patel and published by Springer. This book was released on 2013-10-15 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autism is a complex multifaceted disorder affecting neurodevelopment during the early years of life and, for many, throughout the life span. Inherent features include difficulties or deficits in communication, social interaction, cognition, and interpersonal behavioral coordination, to name just a few. Autism profoundly impacts the affected individual, the family, and, in many cases, the localized communities. The increased prevalence of childhood autism has resulted in rapid developments in a wide range of disciplines in recent years. Nevertheless, despite intensive research, the cause(s) remain unresolved and no single treatment strategy is employed. To address these issues, Comprehensive Guide to Autism is an all-embracing reference that offers analyses and discussions of contemporary issues in the field of autism. The work brings together scientific material from leading experts in the field relating to a wide range of important current topics, such as the early identification and treatment of children with autism, pertinent social and behavioral studies, recent developments in genetics and immunology, the influence of diet, models of autism, and future treatment prospects. Comprehensive Guide to Autism contains essential readings for behavioral science researchers, psychologists, physicians, social workers, parents, and caregivers.

Download or read book Molecular Neuropathology written by Gareth W. Roberts and published by Cambridge University Press. This book was released on 1995-06-08 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides an introduction to the essential techniques required for studying the molecular biology of brain disease. The approaches and strategies for investigations of gene structure and regulation are described with reference to the molecular genetics of prion and Alzheimer's disease. The effects of aberrant gene regulation can also be examined at the protein level by immunocytochemistry and autoradiography. Improved understanding of basic biology has resulted in new approaches to animal models using transgenic techniques and new therapeutic approaches. The volume is structured to illustrate all these approaches and demonstrate the practice and promise of molecular neuropathology.

Download or read book Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability written by Carlo Sala and published by Academic Press. This book was released on 2016-04-30 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability provides the latest information on Autism spectrum disorders (ASDs), the lifelong neurodevelopmental disorders that present in early childhood and affect how individuals communicate and relate to others and their surroundings. In addition, three quarters of ASD patients also manifest severe intellectual disability. Though certain genes have been implicated, ASDs remain largely a mystery, and research looking into causes and cellular deficits are crucial for better understanding of neurodevelopmental disorders. Despite the prevalence and insidious nature of this disorder, this book remains to be an extensive resource of information and background on the state of current research in the field. The book serves as a reference for this purpose, and discusses the crucial role synaptic activity plays in proper brain function. In addition, the volume discusses the neurodevelopmental synaptopathies and serves as a resource for scientists and clinicians in all biomedical science specialties. This research has been crucial for recent studies that have provided a rationale for the development of pharmacological agents able to counteract functional synaptic anomalies and potentially ameliorate some ASD symptoms. Introduces the genetic and non-genetic causes of autism and associated intellectual disabilities Describes the genes implicated in autistic spectrum disorders and their function Considers major individual genetic causes of autism, Rett syndrome, Fragile X syndrome, and other autism spectrum disorders, as well as their classification as synaptopathies Presents a thorough discussion of the clinical aspects of multiple neurodevelopmental disorders and the experimental models that exist to study their pathophysiology in vitro and in vivo, including animal models and patient-derived stem cell culture

Download or read book Jasper s Basic Mechanisms of the Epilepsies written by Jeffrey Noebels and published by OUP USA. This book was released on 2012-06-29 with total page 1258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.

Download or read book The Neuroscience of Autism Spectrum Disorders written by Joseph D. Buxbaum and published by Academic Press. This book was released on 2012-10-25 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autism is no longer considered a rare disease, and the Center for Disease Control now estimates that upwards of 730,000 children in the US struggle with this isolating brain disorder. New research is leading to greater understanding of and ability to treat the disorder at an earlier age. It is hoped that further genetic and imaging studies will lead to biologically based diagnostic techniques that could help speed detection and allow early, more effective intervention. Edited by two leaders in the field, this volume offers a current survey and synthesis of the most important findings of the neuroscience behind autism of the past 20 years. With chapters authored by experts in each topic, the volume explores etiology, neuropathology, imaging, and pathways/models. Offering a broad background of ASDs with a unique focus on neurobiology, the volume offers more than the others on the market with a strictly clinical focus or a single authored perspective that fails to offer expert, comprehensive coverage. Researchers and graduate students alike with an interest in developmental disorders and autism will benefit, as will autism specialists across psychology and medicine looking to expand their expertise. Uniquely explores ASDs from a neurobiological angle, looking to uncover the molecular/cellular basis rather than to merely catalog the commonly used behavioral interventions Comprehensive coverage synthesizes widely dispersed research, serving as one-stop shopping for neurodevelopmental disorder researchers and autism specialists Edited work with chapters authored by leaders in the field around the globe - the broadest, most expert coverage available

Download or read book Cognitive Plasticity in Neurologic Disorders written by Joseph I. Tracy and published by Oxford University Press, USA. This book was released on 2014-12-02 with total page 433 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume makes clear that the cognitive and behavioural symptoms of neurologic disorders and syndromes are dynamic and changing. Each chapter describes the neuroplastic processes at work in a particular condition, giving rise to these ongoing cognitive changes.

Download or read book Excitatory Amino Acids written by Peter H. Seeburg and published by Springer Science & Business Media. This book was released on 2013-03-14 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book emerging questions of current glutamate research are addressed and new pathways which glutamte research may take in the future discussed. Since glutamate antagonists are still the major hope for the therapy of neurodegenerative disorders in humans, research activities dedicated towards the development of such novel drugs are the focus of public attention. The book comments on the most recent discoveries in the field of neuroprotection and neurodegeneration.