scholarly journals Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 358 ◽  
Author(s):  
Diana C. Muñoz-Lasso ◽  
Carlos Romá-Mateo ◽  
Federico V. Pallardó ◽  
Pilar Gonzalez-Cabo
Keyword(s):  
Neurological Disorders ◽  
Actin Filaments ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Three Dimensional ◽  
Cytoskeletal Proteins ◽  
Dimensional Lattice ◽  
New Treatments ◽  
And Function

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.

First person – Fanny Jaudon and Martina Albini

2021 ◽  
Vol 134 (16) ◽  
Keyword(s):  
Neurotrophic Factor ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Early Career ◽  
First Person ◽  
Early Career Researchers ◽  
And Function ◽  
The University ◽  
Selection Of

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.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

2021 ◽  
Vol 10 (16) ◽  
pp. 3554
Author(s):  
Dionysios J. Papachristou ◽  
Stavros Georgopoulos ◽  
Peter V. Giannoudis ◽  
Elias Panagiotopoulos
Keyword(s):  
Fracture Healing ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Healing Process ◽  
Bone Architecture ◽  
Multi Stage ◽  
Stage Process ◽  
And Function ◽  
The Impact

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.

scholarly journals Role of Enzymes in Causing Neurological Disorders

2021 ◽  
Vol 12 (1) ◽  
pp. 466-476
Author(s):  
Vysakh Visweswaran ◽  
Roshni PR
Keyword(s):  
Neurological Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Direct Result ◽  
Permanent Disability ◽  
Genetic Abnormalities ◽  
Underlying Pathology

Diseases of the nervous system are always associated with poor prognosis and limited treatment options. The fragile nature of the neurons and their inability to replicate means that neurological disorders are associated with a permanent disability. Pharmacotherapy of neurological diseases requires understanding the molecular mechanisms involved in the disease pathology. In most of the cases a faulty cellular biochemical pathway is involved, resulting from a defective enzyme. This article focusses on role of enzymes in various neurological disorders. To review pertinent literature and summarise the role of enzymes in the underlying pathology of various neurological disorders. A comprehensive literature search was conducted using PubMed, SCOPUS, J-GATE and Google Scholar and relevant papers were collected using the keywords enzymes, Alzheimer's disease, redox, thiamine, depression, neurotransmitters, epileptogenesis. The literature review highlighted the role of enzymes in major neurological disorders and their potential to be used as drug targets and biomarkers. Identifying defective enzymes gives us new molecular targets to focus on for developing more effective pharmacotherapeutic options. They can be also considered as potential biomarkers. An abnormal enzyme is most often a direct result of an underlying genetic abnormality. Identifying and screening for these genetic abnormalities can be used in early identification and prevention of disease in individuals who have a genetic predisposition. The modern advances in genetic engineering shows a lot of promise in correcting these abnormalities and development of revolutionary cures although ethical concerns remain. 

scholarly journals 3D genome organization during lymphocyte development and activation

2019 ◽  
Vol 19 (2) ◽  
pp. 71-82 ◽  
Author(s):  
Anne van Schoonhoven ◽  
Danny Huylebroeck ◽  
Rudi W Hendriks ◽  
Ralph Stadhouders
Keyword(s):  
Genome Organization ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Lymphocyte Development ◽  
Control Of Gene Expression ◽  
3D Genome ◽  
Wide Range ◽  
3D Architecture

Abstract Chromosomes have a complex three-dimensional (3D) architecture comprising A/B compartments, topologically associating domains and promoter–enhancer interactions. At all these levels, the 3D genome has functional consequences for gene transcription and therefore for cellular identity. The development and activation of lymphocytes involves strict control of gene expression by transcription factors (TFs) operating in a three-dimensionally organized chromatin landscape. As lymphocytes are indispensable for tissue homeostasis and pathogen defense, and aberrant lymphocyte activity is involved in a wide range of human morbidities, acquiring an in-depth understanding of the molecular mechanisms that control lymphocyte identity is highly relevant. Here we review current knowledge of the interplay between 3D genome organization and transcriptional control during B and T lymphocyte development and antigen-dependent activation, placing special emphasis on the role of TFs.

scholarly journals BK Channel Gating Mechanisms: Progresses Toward a Better Understanding of Variants Linked Neurological Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianmin Cui
Keyword(s):  
Neurological Disorders ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Bk Channels ◽  
Bk Channel ◽  
Channel Activation ◽  
Gating Mechanisms ◽  
Intracellular Ca ◽  
Atomistic Structure

The large conductance Ca2+-activated potassium (BK) channel is activated by both membrane potential depolarization and intracellular Ca2+ with distinct mechanisms. Neural physiology is sensitive to the function of BK channels, which is shown by the discoveries of neurological disorders that are associated with BK channel mutations. This article reviews the molecular mechanisms of BK channel activation in response to voltage and Ca2+ binding, including the recent progress since the publication of the atomistic structure of the whole BK channel protein, and the neurological disorders associated with BK channel mutations. These results demonstrate the unique mechanisms of BK channel activation and that these mechanisms are important factors in linking BK channel mutations to neurological disorders.

scholarly journals Retromer Combinatorials for Gene-Therapy Across a Spectrum of Neurological Diseases

2020 ◽  
Author(s):  
Yasir H. Qureshi ◽  
Vivek M. Patel ◽  
Suvarnambiga Kannan ◽  
Samuel D Waksal ◽  
Gregory A. Petsko ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Neurological Disorders ◽  
Viral Vectors ◽  
Neurological Diseases ◽  
Neuroblastoma Cell ◽  
Biological Pathway ◽  
Endosomal Trafficking ◽  
Limited Effect ◽  
And Function ◽  
Neuroblastoma Cell Lines

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.

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
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
The Body ◽  
Normal Brain ◽  
Key Factors ◽  
Therapeutic Outcomes ◽  
Brain Structure And Function ◽  
And Function ◽  
Different Origins ◽  
Frontotemporal Lobar Dementia

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.

scholarly journals Effects of Neurological Disorders on Bone Health

2020 ◽  
Vol 11 ◽  
Author(s):  
Ryan R. Kelly ◽  
Sara J. Sidles ◽  
Amanda C. LaRue
Keyword(s):  
Bone Health ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Sensory Innervation ◽  
Current Evidence ◽  
Bone Homeostasis ◽  
Shared Risk ◽  
The Brain

Neurological diseases, particularly in the context of aging, have serious impacts on quality of life and can negatively affect bone health. The brain-bone axis is critically important for skeletal metabolism, sensory innervation, and endocrine cross-talk between these organs. This review discusses current evidence for the cellular and molecular mechanisms by which various neurological disease categories, including autoimmune, developmental, dementia-related, movement, neuromuscular, stroke, trauma, and psychological, impart changes in bone homeostasis and mass, as well as fracture risk. Likewise, how bone may affect neurological function is discussed. Gaining a better understanding of brain-bone interactions, particularly in patients with underlying neurological disorders, may lead to development of novel therapies and discovery of shared risk factors, as well as highlight the need for broad, whole-health clinical approaches toward treatment.

scholarly journals The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

2021 ◽  
Vol 23 (1) ◽  
pp. 114
Author(s):  
Irina Baichurina ◽  
Victor Valiullin ◽  
Victoria James ◽  
Albert Rizvanov ◽  
Yana Mukhamedshina
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Rna Isolation ◽  
Cord Injury

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.

Sign in / Sign up

Export Citation Format

Share Document