scholarly journals Microglia and astrocyte involvement in neurodegeneration and brain cancer

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Arthur A. Vandenbark ◽  
Halina Offner ◽  
Szymon Matejuk ◽  
Agata Matejuk

AbstractThe brain is unique and the most complex organ of the body, containing neurons and several types of glial cells of different origins and properties that protect and ensure normal brain structure and function. Neurological disorders are the result of a failure of the nervous system multifaceted cellular networks. Although great progress has been made in the understanding of glia involvement in neuropathology, therapeutic outcomes are still not satisfactory. Here, we discuss recent perspectives on the role of microglia and astrocytes in neurological disorders, including the two most common neurodegenerative conditions, Alzheimer disease and progranulin-related frontotemporal lobar dementia, as well as astrocytoma brain tumors. We emphasize key factors of microglia and astrocytic biology such as the highly heterogeneic glial nature strongly dependent on the environment, genetic factors that predispose to certain pathologies and glia senescence that inevitably changes the CNS landscape. Our understanding of diverse glial contributions to neurological diseases can lead advances in glial biology and their functional recovery after CNS malfunction.

2021 ◽  
Vol 134 (16) ◽  

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.


Author(s):  
Fernando Vidal ◽  
Francisco Ortega

The first chapter proposes to trace the distant roots of the cerebral subject to the late seventeenth century, and particularly to debates about the seat of the soul, the corpuscularian theory of matter, and John Locke’s philosophy of personal identity. In the wake of Locke, eighteenth century authors began to assert that the brain is the only part of the body we need to be ourselves. In the nineteenth century, this form of deterministic essentialism contributed to motivate research into brain structure and function, and in turn confirmed the brain-personhood nexus. Since then, from phrenology to functional neuroimaging, neuroscientific knowledge and representations have constituted a powerful support for prescriptive outlooks on the individual and society. “Neuroascesis,” as we call the business that sells programs of cerebral self-discipline, is a case in point, which this chapter also examines. It appeals to the brain and neuroscience as bases for its self-help recipes to enhance memory and reasoning, fight depression, anxiety and compulsions, improve sexual performance, achieve happiness, and even establish a direct contact with God. Yet underneath the neuro surface lie beliefs and even concrete instructions that can be traced to nineteenth-century hygiene manuals.


2020 ◽  
Vol 14 ◽  
Author(s):  
Isis Zhang ◽  
Huijuan Hu

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.


2013 ◽  
pp. 16-22
Author(s):  
Alessandro Castiglione ◽  
Claudia Aimoni ◽  
Giovanni Scanelli

Background: Balance is primarily related to the proper functioning of three sensory input: vestibular, visual and proprioceptive. The integration of these different afferences contributes to the proper attitude of the body in static and dynamic conditions. Equilibrium disorders are common among elderly patients and are responsible for falls and fractures, leading sometimes to catastrophic outcomes, representing a serious health and social problem. Approximately one third of elderly patients at home and about 50% of institutionalized, over 75 year-old, suffer from this particular condition, with at least one fall a year and almost 50% of these with recurrent episodes. Females are more affected than males. Attempts to ascertain the underlying cause of unbalance should be done, leading then to specific treatment. Nevertheless, many elderly patients do not have a single disease but rather a multitude of medical conditions which may cause dizziness, imbalance and vertigo: effects of ageing, drugs, cardiovascular and neurological disorders, ocular and orthopaedic diseases. Aim of the study: A literature review was carried out with the intention to offer practical and useful notions for the management and treatment of equilibrium disorders. Discussion: In clinical practice, the main challenge is to distinguish between peripheral and central imbalance disorders. The data collected from history and clinical exams should be integrated with the intent to include the patient in one of the following clinical conditions: vertiginous syndrome, pre-syncope and/or syncope, neurological diseases, other conditions.Conclusions: Following the differential diagnosis, treatment mainly consists in drug administration (antiemetic and vestibular suppressor drugs) and vestibular rehabilitation (physiotherapy and vestibular exercises).


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 358 ◽  
Author(s):  
Diana C. Muñoz-Lasso ◽  
Carlos Romá-Mateo ◽  
Federico V. Pallardó ◽  
Pilar Gonzalez-Cabo

Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.


Author(s):  
Y. A. Dmitrieva ◽  
I. N. Zakharova ◽  
E. R. Radchenko ◽  
E. A. Doroshina

Gluten represents an alcohol- soluble fraction of endosperm proteins of some cereals (wheat, rye, barley). The molecular characteristics of gluten, in particular, the high content of proline in the composition, determines its high resistance to human gastric, pancreatic and intestinal enzymes. Accordingly, gluten peptides retain their immunogenicity when they enter the internal environment of the body, which determines their ability to activate both the innate and adaptive immune response, and maintain pathological immune- mediated reactions that underlie the complex of gluten- associated diseases and pathological conditions. The question of how gluten consumption may be associated with various neurological disorders continues to be discussed. Despite the lack of sufficient objective evidence, the peculiarities of gliadin metabolism suggest the possibility of an association between the consumption of gluten- containing products with the development of neuropsychiatric disorders.. Of particular interest is the efficacy of gluten-free diet in the complex therapy of such diseases as autism, schizophrenia, as well as some neurological disorders, including chronic fatigue syndrome, various cognitive impairments, depression, etc. The article presents a number of research results, as well as discusses the potential mechanisms of the neurotropic action of gluten. The article discusses the potential metabolic and immunological mechanisms of the neurotropic action of gluten, analyzes the literature data regarding the effectiveness of a gluten-free diet in various neurological diseases and psychiatric disorders.


2020 ◽  
Author(s):  
Yasir H. Qureshi ◽  
Vivek M. Patel ◽  
Suvarnambiga Kannan ◽  
Samuel D Waksal ◽  
Gregory A. Petsko ◽  
...  

ABSTRACTEndosomal trafficking is a biological pathway implicated in Alzheimer’s and Parkinson’s disease, and a growing number of other neurological disorders. For this category of diseases, the endosome’s trafficking complex retromer has emerged as a validated therapeutic target. Retromer’s core is a heterotrimeric complex composed of the scaffold protein VPS35 to which VPS26 and VPS29 bind. Unless it is deficient, increasing expression of VPS35 by viral vectors has a limited effect on other trimeric members and on retromer’s overall function. Here we set out to address these constraints and, based on prior insight, hypothesized that co-expressing VPS35 and VPS26 would synergistically interact and elevate retromer’s trimeric expression and function. Neurons, however, are distinct in expressing two VPS26 paralogs, VPS26a and VPS26b, and so to test the hypothesis we generated three novel AAV9 vectors harboring the VPS35, or VPS26a, or VPS26b transgene. First, we optimized their expression in neuroblastoma cell lines, then, in a comprehensive series of neuronal culture experiments, we expressed VPS35, VPS26a, and VPS26b individually and in all possible combinations. Confirming our hypothesis, expressing individual proteins failed to affect the trimer, while VPS35 and VPS26 combinatorials synergized the trimer’s expression. In addition, we illustrate functional synergy by showing that only VPS35 and VPS26 combinatorials significantly increase levels of Sorl1, a key retromer-receptor deficient in Alzheimer’s disease. Collectively, and together with other recent observations, these results suggest a precision-medicine logic when applying retromer gene therapy to a host of neurological disorders, depending on each disorder’s specific retromer-related molecular and anatomical phenotype.


Author(s):  
Bruce R. Ransom

This resource is the long-awaited new revision of the most highly regarded reference volume on glial cells, and has been completely revised, greatly enlarged, and enhanced with full color figures throughout. Neglected in research for years, it is now evident that the brain only functions in a concerted action of all the cells, namely glia and neurons. Seventy one chapters comprehensively discuss virtually every aspect of normal glial cell anatomy, physiology, biochemistry and function, and consider the central roles of these cells in neurological diseases including stroke, Alzheimer disease, multiple sclerosis, Parkinson's disease, neuropathy, and psychiatric conditions. With more than 20 new chapters it addresses the massive growth of knowledge about the basic biology of glia and the sophisticated manner in which they partner with neurons in the course of normal brain function.


2020 ◽  
Vol 10 (1) ◽  
pp. 56 ◽  
Author(s):  
Kate L. Lambertsen ◽  
Catarina B. Soares ◽  
David Gaist ◽  
Helle H. Nielsen

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.


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