scholarly journals The Role of the Inflammasome in Neurodegenerative Diseases

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 953
Author(s):  
Federica Piancone ◽  
Francesca La Rosa ◽  
Ivana Marventano ◽  
Marina Saresella ◽  
Mario Clerici
Keyword(s):  
Neurodegenerative Diseases ◽  
Nlrp3 Inflammasome ◽  
Adaptor Protein ◽  
Neuronal Structure ◽  
Inflammatory Mechanism ◽  
The Central Nervous System ◽  
And Function ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines

Neurodegenerative diseases are chronic, progressive disorders that occur in the central nervous system (CNS). They are characterized by the loss of neuronal structure and function and are associated with inflammation. Inflammation of the CNS is called neuroinflammation, which has been implicated in most neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Much evidence indicates that these different conditions share a common inflammatory mechanism: the activation of the inflammasome complex in peripheral monocytes and in microglia, with the consequent production of high quantities of the pro-inflammatory cytokines IL-1β and IL-18. Inflammasomes are a group of multimeric signaling complexes that include a sensor Nod-like receptor (NLR) molecule, the adaptor protein ASC, and caspase-1. The NLRP3 inflammasome is currently the best-characterized inflammasome. Multiple signals, which are potentially provided in combination and include endogenous danger signals and pathogens, trigger the formation of an active inflammasome, which, in turn, will stimulate the cleavage and the release of bioactive cytokines including IL-1β and IL-18. In this review, we will summarize results implicating the inflammasome as a pivotal player in the pathogenesis of neurodegenerative diseases and discuss how compounds that hamper the activation of the NLRP3 inflammasome could offer novel therapeutic avenues for these diseases.

scholarly journals Astroglial Connexins in Neurodegenerative Diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Xiaomin Huang ◽  
Yixun Su ◽  
Nan Wang ◽  
Hui Li ◽  
Zhigang Li ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Function ◽  
Gap Junction Channels ◽  
Normal Functions ◽  
Functional Remodeling ◽  
The Central Nervous System ◽  
Key Aspects ◽  
And Function ◽  
Lateral Sclerosis

Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.

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 The Interplay between Ca2+ Signaling Pathways and Neurodegeneration

2019 ◽  
Vol 20 (23) ◽  
pp. 6004 ◽  
Author(s):  
Ureshino ◽  
Erustes ◽  
Bassani ◽  
Wachilewski ◽  
Guarache ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Temporal Organization ◽  
Amyloid Peptide ◽  
Physiological Processes ◽  
Stress Energy ◽  
The Central Nervous System ◽  
Β Amyloid Peptide ◽  
And Function ◽  
Related Proteins

Calcium (Ca2+) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca2+ signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca2+ concentration are needed to transmit information from neuron to neuron, between neurons and glia, and even regulating local blood flow according to the required activity. However, under pathological conditions, Ca2+ homeostasis is altered, with increased cytoplasmic Ca2+ concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca2+ signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca2+ homeostasis depends on coordinated interactions between the endoplasmic reticulum, mitochondria, and lysosomes, as well as specific transport mechanisms. In neurodegenerative diseases, alterations-increased oxidative stress, energy metabolism alterations, and protein aggregation have been identified. The aggregation of α-synuclein, β-amyloid peptide (Aβ), and huntingtin all adversely affect Ca2+ homeostasis. Due to the mounting evidence for the relevance of Ca2+ signaling in neuroprotection, we would focus on the expression and function of Ca2+ signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.

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 Nanoparticles: A Hope for the Treatment of Inflammation in CNS

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng-Dan Zhu ◽  
Yu-Jiao Hu ◽  
Lu Yu ◽  
Xiao-Gang Zhou ◽  
Jian-Ming Wu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Therapeutic Agent ◽  
Therapeutic Effects ◽  
Therapeutic Tool ◽  
Promising Strategy ◽  
The Central Nervous System ◽  
Inflammatory Drugs ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines

Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), among others. The over-activated microglia release pro-inflammatory cytokines, which induces neuronal death and accelerates neurodegeneration. Therefore, inhibition of microglia over-activation and microglia-mediated neuroinflammation has been a promising strategy for the treatment of neurodegenerative diseases. Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood–brain barrier (BBB)—a natural barrier preventing brain tissue from contact with harmful plasma components—seriously hinders drug delivery to the microglial cells in CNS. As an emerging useful therapeutic tool in CNS-related diseases, nanoparticles (NPs) have been widely applied in biomedical fields for use in diagnosis, biosensing and drug delivery. Recently, many NPs have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases.

scholarly journals Is Modulation of Oxidative Stress an Answer? The State of the Art of Redox Therapeutic Actions in Neurodegenerative Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Valerio Chiurchiù ◽  
Antonio Orlacchio ◽  
Mauro Maccarrone
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Neuronal Loss ◽  
Spastic Paraplegia ◽  
The Central Nervous System ◽  
High Production ◽  
The Brain ◽  
Lateral Sclerosis

The central nervous system is particularly sensitive to oxidative stress due to many reasons, including its high oxygen consumption even under basal conditions, high production of reactive oxygen and nitrogen species from specific neurochemical reactions, and the increased deposition of metal ions in the brain with aging. For this reason, along with inflammation, oxidative stress seems to be one of the main inducers of neurodegeneration, causing excitotoxicity, neuronal loss, and axonal damage, ultimately being now considered a key element in the onset and progression of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and hereditary spastic paraplegia. Thus, the present paper reviews the role of oxidative stress and of its mechanistic insights underlying the pathogenesis of these neurodegenerative diseases, with particular focus on current studies on its modulation as a potential and promising therapeutic strategy.

The emerging role of the chondroitin sulfate proteoglycan family in neurodegenerative diseases

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jia-zhe Lin ◽  
Ming-rui Duan ◽  
Nuan Lin ◽  
Wei-jiang Zhao
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Chondroitin Sulfate ◽  
Core Protein ◽  
Chondroitin Sulfate Proteoglycans ◽  
Chondroitin Sulfate Proteoglycan ◽  
The Central Nervous System ◽  
Covalently Linked ◽  
Lateral Sclerosis

Abstract Chondroitin sulfate (CS) is a kind of linear polysaccharide that is covalently linked to proteins to form proteoglycans. Chondroitin sulfate proteoglycans (CSPGs) consist of a core protein, with one or more CS chains covalently attached. CSPGs are precisely regulated and they exert a variety of physiological functions by binding to adhesion molecules and growth factors. Widely distributed in the nervous system in human body, CSPGs contribute to the major component of extracellular matrix (ECM), where they play an important role in the development and maturation of the nervous system, as well as in the pathophysiological response to damage to the central nervous system (CNS). While there are more than 30 types of CSPGs, this review covers the roles of the most important ones, including versican, aggrecan, neurocan and NG2 in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The updated reports of the treatment of neurodegenerative diseases are involving CSPGs.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Understanding the role of Inflammasome in Angina Pectoris

2020 ◽  
Vol 21 ◽  
Author(s):  
Ishita Sharma ◽  
Tapan Behl ◽  
Simona Bungau ◽  
Monika Sachdeva ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Angina Pectoris ◽  
Nlrp3 Inflammasome ◽  
Vital Role ◽  
Death Process ◽  
Cell Death Process ◽  
Artery Disease ◽  
Species Production ◽  
Pro Inflammatory Cytokines

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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