scholarly journals Extracellular Vesicle-Mediated Cell–Cell Communication in the Nervous System: Focus on Neurological Diseases

2019 ◽  
Vol 20 (2) ◽  
pp. 434 ◽  
Author(s):  
Celeste Caruso Bavisotto ◽  
Federica Scalia ◽  
Antonella Marino Gammazza ◽  
Daniela Carlisi ◽  
Fabio Bucchieri ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurological Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Response To Treatment ◽  
Therapeutic Drugs ◽  
The Central Nervous System ◽  
Bioengineering Techniques ◽  
Cell Cell

Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear as promising theranostics elements, applicable to accurately diagnosing pathological conditions, and assessing prognosis and response to treatment in a variety of disorders. Likewise, the characteristics and manageability of exosomes make them potential candidates for delivering selected molecules, e.g., therapeutic drugs, to specific target tissues. All these possible applications are pertinent to research in neurophysiology, as well as to the study of neurological disorders, including CNS tumors, and autoimmune and neurodegenerative diseases. In this brief review, we discuss what is known about the role and potential future applications of exosomes in the nervous system and its diseases, focusing on cell–cell communication in physiology and pathology.

Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System

2017 ◽  
Vol 24 (3) ◽  
pp. 208-220 ◽  
Author(s):  
Pei-Pei Liu ◽  
Ya-Jie Xu ◽  
Zhao-Qian Teng ◽  
Chang-Mei Liu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Regulatory Networks ◽  
Neurological Diseases ◽  
Cell Types ◽  
Brain Cell ◽  
Neuronal Morphology ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
The Central Nervous System

The polycomb repressive complex 2 (PRC2) is responsible for catalyzing both di- and trimethylation of histone H3 at lysine 27 (H3K27me2/3). The subunits of PRC2 are widely expressed in the central nervous system (CNS). PRC2 as well as H3K27me2/3, play distinct roles in neuronal identity, proliferation and differentiation of neural stem/progenitor cells, neuronal morphology, and gliogenesis. Mutations or dysregulations of PRC2 subunits often cause neurological diseases. Therefore, PRC2 might represent a common target of different pathological processes that drive neurodegenerative diseases. A better understanding of the intricate and complex regulatory networks mediated by PRC2 in CNS will help to develop new therapeutic approaches and to generate specific brain cell types for treating neurological diseases.

Mills' syndrome. A clinical case of a rare degenerative pathology of the central nervous system

2020 ◽  
pp. 57-60
Author(s):  
Konstantin Gulyabin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Diseases ◽  
Cortical Atrophy ◽  
Primary Lateral Sclerosis ◽  
System A ◽  
The Central Nervous System ◽  
Primary Lateral ◽  
Lateral Sclerosis ◽  
Mills Syndrome

Mills' syndrome is a rare neurological disorder. Its nosological nature is currently not completely determined. Nevertheless, Mills' syndrome is considered to be a rare variant of the degenerative pathology of the central nervous system – a variant of focal cortical atrophy. The true prevalence of this pathology is unknown, since this condition is more often of a syndrome type, observed in the clinical picture of a number of neurological diseases (primary lateral sclerosis, frontotemporal dementia, etc.) and is less common in isolated form.

scholarly journals Vesicular dysfunction and pathways to neurodegeneration

2021 ◽  
Author(s):  
Patrick A. Lewis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Human Brain ◽  
Cell Viability ◽  
Case Studies ◽  
Neurological Diseases ◽  
The Past ◽  
Cellular Events ◽  
The Central Nervous System ◽  
Cellular Control

Abstract Cellular control of vesicle biology and trafficking is critical for cell viability, with disruption of these pathways within the cells of the central nervous system resulting in neurodegeneration and disease. The past two decades have provided important insights into both the genetic and biological links between vesicle trafficking and neurodegeneration. In this essay, the pathways that have emerged as being critical for neuronal survival in the human brain will be discussed – illustrating the diversity of proteins and cellular events with three molecular case studies drawn from different neurological diseases.

scholarly journals Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Mar Pacheco-Herrero ◽  
Luis O. Soto-Rojas ◽  
Charles R. Harrington ◽  
Yazmin M. Flores-Martinez ◽  
Marcos M. Villegas-Rojas ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Public Health Emergency ◽  
Converting Enzyme ◽  
Neurological Manifestations ◽  
Brain Areas ◽  
Angiotensin Converting Enzyme 2 ◽  
The Central Nervous System

The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

scholarly journals Deletion of the Thrombin Proteolytic Site in Neurofascin 155 Causes Disruption of Nodal and Paranodal Organization

2021 ◽  
Vol 15 ◽  
Author(s):  
Dipankar J. Dutta ◽  
R. Douglas Fields
Keyword(s):  
Nervous System ◽  
Gene Editing ◽  
Cell Types ◽  
Complete Loss ◽  
Spectrometric Analysis ◽  
The Third ◽  
Proteolytic Site ◽  
The Central Nervous System ◽  
Trimolecular Complex ◽  
Unique Domain

In the central nervous system, myelin is attached to the axon in the paranodal region by a trimolecular complex of Neurofascin155 (NF155) in the myelin membrane, interacting with Caspr1 and Contactin1 on the axolemma. Alternative splicing of a single Neurofascin transcript generates several different Neurofascins expressed by several cell types, but NF155, which is expressed by oligodendrocytes, contains a domain in the third fibronectinIII-like region of the molecule that is unique. The immunoglobulin 5–6 domain of NF155 is essential for binding to Contactin1, but less is known about the functions of the NF155-unique third fibronectinIII-like domain. Mutations and autoantibodies to this region are associated with several neurodevelopmental and demyelinating nervous system disorders. Here we used Crispr-Cas9 gene editing to delete a 9 bp sequence of NF155 in this unique domain, which has recently been identified as a thrombin binding site and implicated in plasticity of the myelin sheath. This small deletion results in dysmyelination, eversion of paranodal loops of myelin, substantial enlargement of the nodal gap, a complete loss of paranodal septate junctions, and mislocalization of Caspr1 and nodal sodium channels. The animals exhibit tremor and ataxia, and biochemical and mass spectrometric analysis indicates that while NF155 is transcribed and spliced normally, the NF155 protein is subsequently degraded, resulting in loss of the full length 155 kDa native protein. These findings reveal that this 9 bp region of NF155 in its unique third fibronectinIII-like domain is essential for stability of the protein.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Multifaceted roles of microRNAs: From motor neuron generation in embryos to degeneration in spinal muscular atrophy

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tai-Heng Chen ◽  
Jun-An Chen
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Cell Types ◽  
Spinal Motor Neurons ◽  
Potential Applications ◽  
The Central Nervous System

Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.

Regenerative medicine for neurological diseases—will regenerative neurosurgery deliver?

BMJ ◽  
2021 ◽  
pp. n955
Author(s):  
Terry C Burns ◽  
Alfredo Quinones-Hinojosa
Keyword(s):  
Regenerative Medicine ◽  
Neurological Diseases ◽  
Cell Types ◽  
Ethical Challenges ◽  
Cord Injury ◽  
Practice Of Medicine ◽  
Challenges And Opportunities ◽  
The Central Nervous System ◽  
Future Practice ◽  
Lateral Sclerosis

Abstract Regenerative medicine aspires to transform the future practice of medicine by providing curative, rather than palliative, treatments. Healing the central nervous system (CNS) remains among regenerative medicine’s most highly prized but formidable challenges. “Regenerative neurosurgery” provides access to the CNS or its surrounding structures to preserve or restore neurological function. Pioneering efforts over the past three decades have introduced cells, neurotrophins, and genes with putative regenerative capacity into the CNS to combat neurodegenerative, ischemic, and traumatic diseases. In this review we critically evaluate the rationale, paradigms, and translational progress of regenerative neurosurgery, harnessing access to the CNS to protect, rejuvenate, or replace cell types otherwise irreversibly compromised by neurological disease. We discuss the evidence surrounding fetal, somatic, and pluripotent stem cell derived implants to replace endogenous neuronal and glial cell types and provide trophic support. Neurotrophin based strategies via infusions and gene therapy highlight the motivation to preserve neuronal circuits, the complex fidelity of which cannot be readily recreated. We specifically highlight ongoing translational efforts in Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and spinal cord injury, using these to illustrate the principles, challenges, and opportunities of regenerative neurosurgery. Risks of associated procedures and novel neurosurgical trials are discussed, together with the ethical challenges they pose. After decades of efforts to develop and refine necessary tools and methodologies, regenerative neurosurgery is well positioned to advance treatments for refractory neurological diseases. Strategic multidisciplinary efforts will be critical to harness complementary technologies and maximize mechanistic feedback, accelerating iterative progress toward cures for neurological diseases.

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