scholarly journals The Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2277
Author(s):  
Paulina Pawelec ◽  
Malgorzata Ziemka-Nalecz ◽  
Joanna Sypecka ◽  
Teresa Zalewska
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Brain Disorders ◽  
The Central Nervous System ◽  
Microglial Response ◽  
The Impact ◽  
Insight Into ◽  
Receptor Cx3cr1 ◽  
Disease Specific

Fractalkine (FKN, CX3CL1) is a transmembrane chemokine expressed by neurons in the central nervous system (CNS). CX3CL1 signals through its unique receptor, CX3CR1, that is expressed in microglia. Within the CNS, fractalkine acts as a regulator of microglia activation in response to brain injury or inflammation. During the last decade, there has been a growing interest in the roles that the CX3CL1/CX3CR1 signaling pathway plays in the neuropathology of a diverse array of brain disorders. However, the reported results have proven controversial, indicating that a disruption of the CX3CL1 axis induces a disease-specific microglial response that may have either beneficial or detrimental effects. Therefore, it has become clear that the understanding of neuron-to-glia signals mediated by CX3CL1/CX3CR1 at different stages of diseases could provide new insight into potential therapeutic targets. Hence, the aim of this review is to provide a summary of the literature on the emerging role of CX3CL1 in animal models of some brain disorders.

scholarly journals The gut-microbiota-brain axis in autism: what Drosophila models can offer?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Safa Salim ◽  
Ayesha Banu ◽  
Amira Alwa ◽  
Swetha B. M. Gowda ◽  
Farhan Mohammad
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Autism Spectrum ◽  
Brain Disorders ◽  
Mediated Communication ◽  
The Impact ◽  
Insight Into ◽  
Drosophila Models

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

scholarly journals Metallothionein in Brain Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Juárez-Rebollar ◽  
Camilo Rios ◽  
Concepción Nava-Ruíz ◽  
Marisela Méndez-Armenta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Main Function ◽  
Brain Disorders ◽  
Essential Metals ◽  
The Central Nervous System

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

scholarly journals Long Non-coding RNAs Associated with Brain Disorders: A Literature Review

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Arash Abdolmaleki ◽  
Sevin Ferdowsi ◽  
Asadollah Asadi ◽  
Yassin Panahi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Literature Review ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Brain Disorders ◽  
Parkinson’S Diseases ◽  
The Central Nervous System ◽  
Non Coding Rnas

Context: Neurodegenerative diseases (NDs) are neurological disorders characterized by the degeneration of the central nervous system (CNS). Studies have examined interactions between long non-coding RNAs (lncRNAs) and functioning of the CNS in NDs. In this study, we summarized the role of different lncRNAs in most NDs. Methods: In this study, different papers published between years 2003 and 2020 were reviewed. Results: LncRNAs can play a significant role in the development of brain disorders. Conclusions: The dysregulation of lncRNAs has been shown to affect NDs such as Alzheimer's disease (AD) and Parkinson’s diseases (PD). In this review, we compiled recent findings related to the main lncRNAs associated with brain disorders.

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 Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Bollaerts ◽  
Jessie Van houcke ◽  
Lien Andries ◽  
Lies De Groef ◽  
Lieve Moons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Current Knowledge ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

scholarly journals Features of nervous system damage in antiphospholipid syndrome

2021 ◽  
Vol 15 (4) ◽  
pp. 404-414
Author(s):  
O. N. Voskresenskaya ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
T. A. Sukontseva ◽  
M. V. Tretyakova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Antiphospholipid Syndrome ◽  
Neurological Disorders ◽  
Molecular Mimicry ◽  
Transverse Myelitis ◽  
Autoimmune Process ◽  
The Central Nervous System ◽  
Interdisciplinary Interaction

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

scholarly journals Oligodendrocyte Bioenergetics in Health and Disease

2018 ◽  
Vol 25 (4) ◽  
pp. 334-343 ◽  
Author(s):  
Lauren Rosko ◽  
Victoria N. Smith ◽  
Reiji Yamazaki ◽  
Jeffrey K. Huang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Energy ◽  
The Body ◽  
Metabolic Coupling ◽  
Energy Demands ◽  
Metabolic Role ◽  
The Central Nervous System ◽  
The Impact

The human brain weighs approximately 2% of the body; however, it consumes about 20% of a person’s total energy intake. Cellular bioenergetics in the central nervous system involves a delicate balance between biochemical processes engaged in energy conversion and those responsible for respiration. Neurons have high energy demands, which rely on metabolic coupling with glia, such as with oligodendrocytes and astrocytes. It has been well established that astrocytes recycle and transport glutamine to neurons to make the essential neurotransmitters, glutamate and GABA, as well as shuttle lactate to support energy synthesis in neurons. However, the metabolic role of oligodendrocytes in the central nervous system is less clear. In this review, we discuss the energetic demands of oligodendrocytes in their survival and maturation, the impact of altered oligodendrocyte energetics on disease pathology, and the role of energetic metabolites, taurine, creatine, N-acetylaspartate, and biotin, in regulating oligodendrocyte function.

scholarly journals Pericytes for Therapeutic Approaches to Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Cao ◽  
Yanbo Zhou ◽  
Mengguang Chen ◽  
Li Li ◽  
Wei Zhang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neurovascular Unit ◽  
Therapeutic Approaches ◽  
Multipotent Cells ◽  
The Central Nervous System

Pericytes are perivascular multipotent cells located on capillaries. Although pericytes are discovered in the nineteenth century, recent studies have found that pericytes play an important role in maintaining the blood—brain barrier (BBB) and regulating the neurovascular system. In the neurovascular unit, pericytes perform their functions by coordinating the crosstalk between endothelial, glial, and neuronal cells. Dysfunction of pericytes can lead to a variety of diseases, including stroke and other neurological disorders. Recent studies have suggested that pericytes can serve as a therapeutic target in ischemic stroke. In this review, we first summarize the biology and functions of pericytes in the central nervous system. Then, we focus on the role of dysfunctional pericytes in the pathogenesis of ischemic stroke. Finally, we discuss new therapies for ischemic stroke based on targeting pericytes.

scholarly journals Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin P. Passaro ◽  
Abraham L. Lebos ◽  
Yao Yao ◽  
Steven L. Stice
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Disorders ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Traditional Approaches ◽  
The Impact ◽  
Neurological Pathology

Neuroinflammation is a key component of neurological disorders and is an important therapeutic target; however, immunotherapies have been largely unsuccessful. In cases where these therapies have succeeded, particularly multiple sclerosis, they have primarily focused on one aspect of the disease and leave room for improvement. More recently, the impact of the peripheral immune system is being recognized, since it has become evident that the central nervous system is not immune-privileged, as once thought. In this review, we highlight key interactions between central and peripheral immune cells in neurological disorders. While traditional approaches have examined these systems separately, the immune responses and processes in neurological disorders consist of substantial crosstalk between cells of the central and peripheral immune systems. Here, we provide an overview of major immune effector cells and the role of the blood-brain barrier in regard to neurological disorders and provide examples of this crosstalk in various disorders, including stroke and traumatic brain injury, multiple sclerosis, neurodegenerative diseases, and brain cancer. Finally, we propose targeting central-peripheral immune interactions as a potential improved therapeutic strategy to overcome failures in clinical translation.

scholarly journals Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload in Zip14−/− Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6773
Author(s):  
Yuze Wu ◽  
Guojun Wei ◽  
Ningning Zhao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Small Intestine ◽  
Neurological Disorders ◽  
The Body ◽  
Future Studies ◽  
The Central Nervous System ◽  
Manganese Transport ◽  
The Brain ◽  
Insight Into

As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14−/− mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14−/− mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans.

Sign in / Sign up

Export Citation Format

Share Document