scholarly journals Cyanobacterial Neurotoxin Beta-Methyl-Amino-l-Alanine Affects Dopaminergic Neurons in Optic Ganglia and Brain of Daphnia magna

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 527 ◽  
Author(s):  
Megan Brooke-Jones ◽  
Martina Gáliková ◽  
Heinrich Dircksen
Keyword(s):  
Neurodegenerative Diseases ◽  
Daphnia Magna ◽  
Dopaminergic Neurons ◽  
Dopaminergic System ◽  
Zooplankton Species ◽  
Form Part ◽  
Aquatic Food ◽  
The Brain ◽  
Offspring Mortality ◽  
Lateral Sclerosis

The non-proteinogenic amino acid beta-methyl-amino-l-alanine (BMAA) is a neurotoxin produced by cyanobacteria. BMAA accumulation in the brain of animals via biomagnification along the food web can contribute to the development of neurodegenerative diseases such as Amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC), the latter being associated with a loss of dopaminergic neurons. Daphnia magna is an important microcrustacean zooplankton species that plays a key role in aquatic food webs, and BMAA-producing cyanobacteria often form part of their diet. Here, we tested the effects of BMAA on putative neurodegeneration of newly identified specific dopaminergic neurons in the optic ganglia/brain complex of D. magna using quantitative tyrosine-hydroxylase immunohistochemistry and fluorescence cytometry. The dopaminergic system was analysed in fed and starved isogenic D. magna adults incubated under different BMAA concentrations over 4 days. Increased BMAA concentration showed significant decrease in the stainability of dopaminergic neurons of D. magna, with fed animals showing a more extreme loss. Furthermore, higher BMAA concentrations tended to increase offspring mortality during incubation. These results are indicative of ingested BMAA causing neurodegeneration of dopaminergic neurons in D. magna and adversely affecting reproduction. This may imply similar effects of BMAA on known human neurodegenerative diseases involving dopaminergic neurons.

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 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.

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 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.

scholarly journals Models for LRRK2-Linked Parkinsonism

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Tianxia Li ◽  
DeJun Yang ◽  
Sarah Sushchky ◽  
Zhaohui Liu ◽  
Wanli W. Smith
Keyword(s):  
Dopaminergic Neurons ◽  
Autosomal Dominant ◽  
Dopaminergic System ◽  
Late Onset ◽  
Lewy Bodies ◽  
Leucine Rich Repeat ◽  
Protein Deposition ◽  
Lrrk2 Gene ◽  
The Brain ◽  
Potential Therapeutics

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD is not fully understood, but it appears to involve both genetic susceptibility and environmental factors. Treatment for PD that prevents neuronal death progression in the dopaminergic system and abnormal protein deposition in the brain is not yet available. Recently, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified to cause autosomal-dominant late-onset PD and contribute to sporadic PD. Here, we review the recent models for LRRK2-linked Parkinsonism and their utility in studying LRRK2 neurobiology, pathogenesis, and potential therapeutics.

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 A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3168
Author(s):  
Serena Silvestro ◽  
Cinzia Sindona ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Phosphorylation ◽  
Neurodegenerative Diseases ◽  
Neuronal Cells ◽  
Antioxidant Properties ◽  
Neuroprotective Effects ◽  
Energy Needs ◽  
Anti Oxidant ◽  
Therapeutic Properties ◽  
The Brain ◽  
Lateral Sclerosis

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.

scholarly journals P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 5996
Author(s):  
Peter Illes
Keyword(s):  
Neurodegenerative Diseases ◽  
Life Quality ◽  
Bioactive Molecules ◽  
Cellular Damage ◽  
P2x7 Receptors ◽  
The Brain ◽  
Intracellular Ions ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines ◽  
Receptor Channel

ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population.

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