scholarly journals Intersection between Redox Homeostasis and Autophagy: Valuable Insights into Neurodegeneration

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 694
Author(s):  
Hyungsun Park ◽  
Jongyoon Kim ◽  
Chihoon Shin ◽  
Seongju Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Redox Homeostasis ◽  
Degradation Pathway ◽  
Pharmacological Intervention ◽  
Oxygen Species ◽  
Promising Strategy ◽  
Autophagy Induction ◽  
The Relationship ◽  
The Brain ◽  
Lateral Sclerosis

Autophagy, a main degradation pathway for maintaining cellular homeostasis, and redox homeostasis have recently been considered to play protective roles in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Increased levels of reactive oxygen species (ROS) in neurons can induce mitochondrial damage and protein aggregation, thereby resulting in neurodegeneration. Oxidative stress is one of the major activation signals for the induction of autophagy. Upon activation, autophagy can remove ROS, damaged mitochondria, and aggregated proteins from the cells. Thus, autophagy can be an effective strategy to maintain redox homeostasis in the brain. However, the interaction between redox homeostasis and autophagy is not clearly elucidated. In this review, we discuss recent studies on the relationship between redox homeostasis and autophagy associated with neurodegenerative diseases and propose that autophagy induction through pharmacological intervention or genetic activation might be a promising strategy to treat these disorders.

scholarly journals Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

2009 ◽  
Vol 45 (4) ◽  
pp. 607-618 ◽  
Author(s):  
Graciela Cristina dos Santos ◽  
Lusânia Maria Greggi Antunes ◽  
Antonio Cardozo dos Santos ◽  
Maria de Lourdes Pires Bianchi
Keyword(s):  
Neurodegenerative Diseases ◽  
Health Risks ◽  
Coenzyme Q10 ◽  
Cellular Respiration ◽  
Irreversible Loss ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Electron Transportation ◽  
The Brain ◽  
Lateral Sclerosis

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

ATP-binding cassette transporters and neurodegenerative diseases

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Abc Transporters ◽  
Brain Diseases ◽  
Atp Binding ◽  
Future Directions ◽  
Diverse Range ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

scholarly journals Radon Exposure and Neurodegenerative Disease

2020 ◽  
Vol 17 (20) ◽  
pp. 7439
Author(s):  
Silvia Gómez-Anca ◽  
Juan Miguel Barros-Dios
Keyword(s):  
Neurodegenerative Diseases ◽  
Scientific Evidence ◽  
Subsequent Development ◽  
Brain Anatomy ◽  
Inclusion Criteria ◽  
Motor Neuron Diseases ◽  
Radon Exposure ◽  
Bibliographic Search ◽  
The Brain ◽  
Lateral Sclerosis

Background: To carry out a systematic review of scientific literature about the association between radon exposure and neurodegenerative diseases. Methods: We performed a bibliographic search in the following databases: Pub med (Medline), Cochrane, BioMed Central and Web of Science. We collected the data by following a predetermined search strategy in which several terms werecombined. After an initial search, 77 articles were obtained.10 of which fulfilled the inclusion criteria. Five of these 10 studies were related to multiple sclerosis (MS), 2 were about motor neuron diseases (MND), in particular amyotrophic lateral sclerosis (ALS) and 3 were related to both Alzheimer’s disease (AD) and Parkinson’s disease (PD). Results: The majority of the included articles, suggested a possible association between radon exposure and a subsequent development of neurodegenerative diseases. Some of the studies that obtained statistically significant resultsrevealed a possible association between radon exposure and an increase in MS prevalence. Furthermore, it was also suggested that radon exposure increases MND and AD mortality. Regarding AD and PD, it was observed that certainde cay products of radon-222 (222Rn), specifically polonium-210 (210Po) and bismuth-210 (210Bi), present a characteristic distributionpattern within the brain anatomy. However, the study with the highest scientific evidence included in this review, which investigated a possible association between the concentration of residential radon gas and the MS incidence, revealed no significant results. Conclusions: It cannot be concluded, although it is observed, that there is a possible causal association between radon exposure and neurodegenerative diseases. Most of the available studies are ecological so, studies of higher statistical evidence are needed to establish a causal relationship. Further research is needed on this topic.

scholarly journals Ferroptosis and Brain Injury

2018 ◽  
Vol 40 (5-6) ◽  
pp. 382-395 ◽  
Author(s):  
Leslie Magtanong ◽  
Scott J. Dixon
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Brain Injuries ◽  
Basic Problem ◽  
Oxygen Species ◽  
Brain Disorders ◽  
Small Molecule Screening ◽  
The Relationship ◽  
The Brain

Ferroptosis is a nonapoptotic form of cell death characterized by the iron-dependent accumulation of toxic lipid reactive oxygen species. Small-molecule screening and subsequent optimization have yielded potent and specific activators and inhibitors of this process. These compounds have been employed to dissect the lethal mechanism and implicate this process in pathological cell death events observed in many tissues, including the brain. Indeed, ferroptosis is emerging as an important mechanism of cell death during stroke, intracerebral hemorrhage, and other acute brain injuries, and may also play a role in certain degenerative brain disorders. Outstanding issues include the practical need to identify molecular markers of ferroptosis that can be used to detect and study this process in vivo, and the more basic problem of understanding the relationship between ferroptosis and other forms of cell death that can be triggered in the brain during injury.

scholarly journals Cerebral sterile inflammation in neurodegenerative diseases

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Kento Otani ◽  
Takashi Shichita
Keyword(s):  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Sterile Inflammation ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Abnormal Accumulation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractTherapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism

2018 ◽  
Vol 17 (8) ◽  
pp. 595-603 ◽  
Author(s):  
Nurul ‘Ain Arshad ◽  
Teoh Seong Lin ◽  
Mohamad Fairuz Yahaya
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Neurodegenerative Diseases ◽  
Disease Type ◽  
Low Grade ◽  
Oxygen Species ◽  
Metabolic Factors ◽  
Low Grade Inflammation ◽  
The Brain

Background & Objective: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer’s disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease. Conclusion: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.

scholarly journals Neurodegenerative disorders and sterile inflammation: lessons from a Drosophila model

2019 ◽  
Vol 166 (3) ◽  
pp. 213-221 ◽  
Author(s):  
Firzan Nainu ◽  
Emil Salim ◽  
Rangga Meidianto Asri ◽  
Aki Hori ◽  
Takayuki Kuraishi
Keyword(s):  
Neurodegenerative Diseases ◽  
Inflammatory Responses ◽  
Biological Significance ◽  
Sterile Inflammation ◽  
Medical Interventions ◽  
Drosophila Model ◽  
Progressive Neurodegeneration ◽  
Molecular Patterns ◽  
The Brain ◽  
Lateral Sclerosis

Abstract Central nervous system (CNS)-related disorders, including neurodegenerative diseases, are common but difficult to treat. As effective medical interventions are limited, those diseases will likely continue adversely affecting people’s health. There is evidence that the hyperactivation of innate immunity is a hallmark of most neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and polyglutamine diseases. In mammalian and fly CNS, the presence of noninfectious ligands, including danger-associated molecular patterns, is recognized by (micro)glial cells, inducing the expression of proinflammatory cytokines. Such inflammation may contribute to the onset and progression of neurodegenerative states. Studies using fruit flies have shed light on the types of signals, receptors and cells responsible for inducing the inflammation that leads to neurodegeneration. Researchers are using fly models to assess the mechanisms of sterile inflammation in the brain and its link to progressive neurodegeneration. Given the similarity of its physiological system and biochemical function to those of mammals, especially in activating and regulating innate immune signalling, Drosophila can be a versatile model system for studying the mechanisms and biological significance of sterile inflammatory responses in the pathogenesis of neurodegenerative diseases. Such knowledge would greatly facilitate the quest for a novel effective treatment for neurodegenerative diseases.

scholarly journals Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyuk Sung Kwon ◽  
Seong-Ho Koh
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Drugs ◽  
M1 Phenotype ◽  
The Central Nervous System ◽  
The Relationship ◽  
Lateral Sclerosis ◽  
M2 Phenotype

AbstractNeuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.

scholarly journals Glutathione in the Brain

2021 ◽  
Vol 22 (9) ◽  
pp. 5010
Author(s):  
Koji Aoyama
Keyword(s):  
Neurodegenerative Diseases ◽  
Regulatory Mechanism ◽  
Excitatory Amino Acid ◽  
Redox Homeostasis ◽  
Disease Onset ◽  
Glutamate Transporter ◽  
Antioxidant Defense System ◽  
Common Finding ◽  
Potential Therapeutic Application ◽  
The Brain

Glutathione (GSH) is the most abundant non-protein thiol, and plays crucial roles in the antioxidant defense system and the maintenance of redox homeostasis in neurons. GSH depletion in the brain is a common finding in patients with neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and can cause neurodegeneration prior to disease onset. Excitatory amino acid carrier 1 (EAAC1), a sodium-dependent glutamate/cysteine transporter that is selectively present in neurons, plays a central role in the regulation of neuronal GSH production. The expression of EAAC1 is posttranslationally controlled by the glutamate transporter-associated protein 3–18 (GTRAP3-18) or miR-96-5p in neurons. The regulatory mechanism of neuronal GSH production mediated by EAAC1 may be a new target in therapeutic strategies for these neurodegenerative diseases. This review describes the regulatory mechanism of neuronal GSH production and its potential therapeutic application in the treatment of neurodegenerative diseases.

scholarly journals Altered Blood-Brain Barrier and Blood-Spinal Cord Barrier Dynamics in Amyotrophic Lateral Sclerosis: Impact on Medication Efficacy and Safety

2021 ◽  
Author(s):  
Yijun Pan ◽  
Joseph Nicolazzo
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Large Body ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Spinal Cord Barrier ◽  
The Brain ◽  
Lateral Sclerosis

The access of drugs into the central nervous system (CNS) is regulated by the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). A large body of evidence supports perturbation of these barriers in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Modifications to the BBB and BSCB are also reported in amyotrophic lateral sclerosis (ALS), albeit these modifications have received less attention relative to those in other neurodegenerative diseases. Such alterations to the BBB and BSCB have the potential to impact on CNS exposure of drugs in ALS, modulating the effectiveness of drugs intended to reach the brain and the toxicity of drugs that are not intended to reach the brain. Given the clinical importance of these phenomena, this review will summarise reported modifications to the BBB and BSCB in ALS, discuss their impact on CNS drug exposure and suggest further research directions so as to optimise medicine use in people with ALS.

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