scholarly journals The Emerging Role of Neural Cell-Derived Exosomes in Intercellular Communication in Health and Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Luyao Huo ◽  
Xinzhe Du ◽  
Xinrong Li ◽  
Sha Liu ◽  
Yong Xu
Keyword(s):  
Neurodegenerative Diseases ◽  
Intercellular Communication ◽  
Neural Cells ◽  
Stress Effect ◽  
Brain Growth ◽  
Bioactive Substances ◽  
Pathological Conditions ◽  
Specific Proteins ◽  
The Central Nervous System

Intercellular communication in the central nervous system (CNS) is essential for brain growth, development, and homeostasis maintenance and, when dysfunctional, is involved in the occurrence and development of neurodegenerative diseases. Increasing evidence indicates that extracellular vesicles, especially exosomes, are critical mediators of intercellular signal transduction. Under physiological and pathological conditions, neural cells secret exosomes with the influence of many factors. These exosomes can carry specific proteins, lipids, nucleic acids, and other bioactive substances to the recipient cells to regulate their function. Depending on the CNS environment, as well as the origin and physiological or pathological status of parental cells, exosomes can mediate a variety of different effects, including synaptic plasticity, nutritional metabolic support, nerve regeneration, inflammatory response, anti-stress effect, cellular waste disposal, and the propagation of toxic components, playing an important role in health and neurodegenerative diseases. This review will discuss the possible roles of exosomes in CNS intercellular communication in both physiologic and neurodegenerative conditions.

scholarly journals The Role of GPNMB in Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Saade ◽  
Giovanna Araujo de Souza ◽  
Cristoforo Scavone ◽  
Paula Fernanda Kinoshita
Keyword(s):  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Published Evidence ◽  
The Central Nervous System ◽  
Inflammation Resolution ◽  
The Brain ◽  
Lps Treatment

Inflammation is a response to a lesion in the tissue or infection. This process occurs in a specific manner in the central nervous system and is called neuroinflammation, which is involved in neurodegenerative diseases. GPNMB, an endogenous glycoprotein, has been recently related to inflammation and neuroinflammation. GPNMB is highly expressed in macrophages and microglia, which are cells involved with innate immune response in the periphery and the brain, respectively. Some studies have shown increased levels of GPNMB in pro-inflammatory conditions, such as LPS treatment, and in pathological conditions, such as neurodegenerative diseases and cancer. However, the role of GPNMB in inflammation is still not clear. Even though most studies suggest that GPNMB might have an anti-inflammatory role by promoting inflammation resolution, there is evidence that GPNMB could be pro-inflammatory. In this review, we gather and discuss the published evidence regarding this interaction.

scholarly journals Exosomes: Innocent Bystanders or Critical Culprits in Neurodegenerative Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Margarida Beatriz ◽  
Rita Vilaça ◽  
Carla Lopes
Keyword(s):  
Neurodegenerative Diseases ◽  
Intercellular Communication ◽  
Prion Diseases ◽  
Genetic Material ◽  
Cell Communication ◽  
Protein Aggregates ◽  
Potential Benefits ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Extracellular vesicles (EVs) are nano-sized membrane-enclosed particles released by cells that participate in intercellular communication through the transfer of biologic material. EVs include exosomes that are small vesicles that were initially associated with the disposal of cellular garbage; however, recent findings point toward a function as natural carriers of a wide variety of genetic material and proteins. Indeed, exosomes are vesicle mediators of intercellular communication and maintenance of cellular homeostasis. The role of exosomes in health and age-associated diseases is far from being understood, but recent evidence implicates exosomes as causative players in the spread of neurodegenerative diseases. Cells from the central nervous system (CNS) use exosomes as a strategy not only to eliminate membranes, toxic proteins, and RNA species but also to mediate short and long cell-to-cell communication as carriers of important messengers and signals. The accumulation of protein aggregates is a common pathological hallmark in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. Protein aggregates can be removed and delivered to degradation by the endo-lysosomal pathway or can be incorporated in multivesicular bodies (MVBs) that are further released to the extracellular space as exosomes. Because exosome transport damaged cellular material, this eventually contributes to the spread of pathological misfolded proteins within the brain, thus promoting the neurodegeneration process. In this review, we focus on the role of exosomes in CNS homeostasis, their possible contribution to the development of neurodegenerative diseases, the usefulness of exosome cargo as biomarkers of disease, and the potential benefits of plasma circulating CNS-derived exosomes.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

Extracellular vesicles, stem cells and the role of miRNAs in neurodegeneration

2021 ◽  
Vol 19 ◽  
Author(s):  
Ayaz M. Belkozhayev ◽  
Minnatallah Al-Yozbaki ◽  
Alex George ◽  
Raigul Ye Niyazova ◽  
Kamalidin O. Sharipov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Direct Consequence ◽  
Therapeutic Benefit ◽  
The Body ◽  
A Cell ◽  
Crucial Information

There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington’s disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

scholarly journals Exploring the Use of Dimethyl Fumarate as Microglia Modulator for Neurodegenerative Diseases Treatment

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 700
Author(s):  
Maria Rosito ◽  
Claudia Testi ◽  
Giacomo Parisi ◽  
Barbara Cortese ◽  
Paola Baiocco ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Iron Homeostasis ◽  
Brain Injuries ◽  
Neuroprotective Effect ◽  
Redox Homeostasis ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Fumaric Acid Ester ◽  
The Central Nervous System

The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression.

scholarly journals Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation

2019 ◽  
Vol 127 (2) ◽  
pp. 645-653 ◽  
Author(s):  
Ivan J. Vechetti
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Vesicles ◽  
Human Body ◽  
Intercellular Communication ◽  
Skeletal Muscle Mass ◽  
Genetic Material ◽  
Muscle Adaptation ◽  
Pathological Conditions ◽  
Isolation Methods

Extracellular vesicles (EVs) were initially characterized as “garbage bags” with the purpose of removing unwanted material from cells. It is now becoming clear that EVs mediate intercellular communication between distant cells through a transfer of genetic material, a process important to the systemic adaptation in physiological and pathological conditions. Although speculative, it has been suggested that the majority of EVs that make it into the bloodstream would be coming from skeletal muscle, since it is one of the largest organs in the human body. Although it is well established that skeletal muscle secretes peptides (currently known as myokines) into the bloodstream, the notion that skeletal muscle releases EVs is in its infancy. Besides intercellular communication and systemic adaptation, EV release could represent the mechanism by which muscle adapts to certain stimuli. This review summarizes the current understanding of EV biology and biogenesis and current isolation methods and briefly discusses the possible role EVs have in regulating skeletal muscle mass.

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 NGF, Brain and Behavioral Plasticity

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Berry ◽  
Erika Bindocci ◽  
Enrico Alleva
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Behavioral Plasticity ◽  
The Body ◽  
Trophic Factor ◽  
Brain Growth ◽  
Male Mice ◽  
Psychosocial Stressor ◽  
The Central Nervous System

Nerve Growth Factor (NGF) was initially studied for its role as a key player in the regulation of peripheral innervations. However, the successive finding of its release in the bloodstream of male mice following aggressive encounters and its presence in the central nervous system led to the hypothesis that variations in brain NGF levels, caused by psychosocial stressor, and the related alterations in emotionality, could be functional to the development of proper strategies to cope with the stressor itself and thus to survive. Years later this vision is still relevant, and the body of evidence on the role of NGF has been strengthened and expanded from trophic factor playing a role in brain growth and differentiation to a much more complex messenger, involved in psychoneuroendocrine plasticity.

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
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