scholarly journals Microglia Mediated Neuroinflammation: Focus on PI3K Modulation

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 137 ◽  
Author(s):  
Antonia Cianciulli ◽  
Chiara Porro ◽  
Rosa Calvello ◽  
Teresa Trotta ◽  
Dario Domenico Lofrumento ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Tissue Damage ◽  
Therapeutic Strategies ◽  
Focused Attention ◽  
Pathogen Invasion ◽  
Wide Range ◽  
Inflammatory Processes ◽  
The Central Nervous System

Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.

scholarly journals The Role of Metals in Neurodegenerative Diseases of the Central Nervous System

2020 ◽  
Vol 8 (2) ◽  
pp. 130-146
Author(s):  
Afshin Montazeri ◽  
Milad Akhlaghi ◽  
Ahmad Reza Barahimi ◽  
Ali Jahanbazi Jahan Abad ◽  
Reza Jabbari ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
The Central Nervous System

scholarly journals The Role of Microglia in the Development of Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1449
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Seong-Man Kim ◽  
Jae-Hong Min ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Therapeutic Strategy ◽  
Experimental Animal Models ◽  
Effective Therapeutic Strategy ◽  
The Central Nervous System ◽  
Animal Models Of Epilepsy ◽  
Models Of Epilepsy

Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

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 Role of Connexins 30, 36, and 43 in Brain Tumors, Neurodegenerative Diseases, and Neuroprotection

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 846 ◽  
Author(s):  
Oscar F. Sánchez ◽  
Andrea V. Rodríguez ◽  
José M. Velasco-España ◽  
Laura C. Murillo ◽  
Jhon-Jairo Sutachan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Cell Communication ◽  
Normal Function ◽  
Epigenetic Mechanisms ◽  
Communication Processes ◽  
The Central Nervous System

Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.

scholarly journals The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches

2021 ◽  
Vol 22 (9) ◽  
pp. 4630
Author(s):  
Agnieszka Kulczyńska-Przybik ◽  
Piotr Mroczko ◽  
Maciej Dulewicz ◽  
Barbara Mroczko
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Pleiotropic Functions ◽  
Lateral Sclerosis

Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.

scholarly journals Living Proof of Activity of Extracellular Vesicles in the Central Nervous System

2021 ◽  
Vol 22 (14) ◽  
pp. 7294
Author(s):  
Shadi Mahjoum ◽  
David Rufino-Ramos ◽  
Luís Pereira de Almeida ◽  
Marike L. D. Broekman ◽  
Xandra O. Breakefield ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Optimal Functioning ◽  
Wide Range ◽  
The Central Nervous System ◽  
Rna And Dna

The central nervous system (CNS) consists of a heterogeneous population of cells with highly specialized functions. For optimal functioning of the CNS, in disease and in health, intricate communication between these cells is vital. One important mechanism of cellular communication is the release and uptake of extracellular vesicles (EVs). EVs are membrane enclosed particles actively released by cells, containing a wide array of proteins, lipids, RNA, and DNA. These EVs can be taken up by neighboring or distant cells, and influence a wide range of processes. Due to the complexity and relative inaccessibility of the CNS, our current understanding of the role of EVs is mainly derived in vitro work. However, recently new methods and techniques have opened the ability to study the role of EVs in the CNS in vivo. In this review, we discuss the current developments in our understanding of the role of EVs in the CNS in vivo.

scholarly journals Neuroinflammation: A Potential Risk for Dementia

2022 ◽  
Vol 23 (2) ◽  
pp. 616
Author(s):  
Md Afroz Ahmad ◽  
Ozaifa Kareem ◽  
Mohammad Khushtar ◽  
Md Akbar ◽  
Md Rafiul Haque ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Activation ◽  
Microglial Cell ◽  
Oxygen Species ◽  
Independent Function ◽  
Published Evidence ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
The Brain

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain’s immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell’s microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

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 The Role of ACE2 Receptors of the Olfactory System in Anosmia in COVID-19: An Overview

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Mohammad Javad Nasr ◽  
Ali Alizadeh Khatir ◽  
Arefeh Babazadeh ◽  
Soheil Ebrahimpour
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Severe Acute Respiratory Syndrome ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Complete Loss ◽  
Loss Of Consciousness ◽  
Wide Range ◽  
The Central Nervous System

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). The latest data show that more than 211.7 million people were infected and more than 4.4 million deaths have been reported. The illness presents a wide range of symptoms, ranging from mild to severe. Mild symptoms include cough, fever, dyspnea, fatigue, myalgia and arthralgia, anosmia, and dysgeusia. Furthermore, this virus can affect the central nervous system (CNS) and present a range of mild to severe nervous symptoms, from headache and dysphoria to loss of consciousness, coma, paralysis, and acute cerebrovascular disease. The virus can enter nonneuronal cells of the olfactory epithelium and cause a complete loss of smell. Anosmia and hyposmia are commonly reported in clinics, and being asymptomatic or showing mild symptoms can be primary symptoms in early infected persons. Dysgeusia/hypogeusia is another symptom presented with anosmia/hyposmia. In this article, we reviewed the articles of anosmia and suggested a possible mechanism for this.

scholarly journals New Insights into the Role of Cysteine Cathepsins in Neuroinflammation

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1796
Author(s):  
Anja Pišlar ◽  
Lara Bolčina ◽  
Janko Kos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Neuronal Death ◽  
Early Stage ◽  
Signaling Cascade ◽  
Functional Roles ◽  
Cysteine Cathepsins ◽  
The Central Nervous System

Neuroinflammation, which is mediated by microglia and astrocytes, is associated with the progression of neurodegenerative diseases. Increasing evidence shows that activated microglia induce the expression and secretion of various lysosomal cathepsins, particularly during the early stage of neuroinflammation. This trigger signaling cascade that aggravate neurodegeneration. To date, most research on neuroinflammation has focused on the role of cysteine cathepsins, the largest cathepsin family. Cysteine cathepsins are primarily responsible for protein degradation in lysosomes; however, they also play a role in regulating a number of other important physiological and pathological processes. This review focuses on the functional roles of cysteine cathepsins in the central nervous system during neuroinflammation, with an emphasis on their roles in the polarization of microglia and neuroinflammation signaling, which in turn causes neuronal death and thus neurodegeneration.

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