scholarly journals Metals and Neurodegeneration

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 366 ◽  
Author(s):  
Pan Chen ◽  
Mahfuzur Rahman Miah ◽  
Michael Aschner
Keyword(s):  
Metal Accumulation ◽  
Neurological Diseases ◽  
Cell Structure ◽  
Antioxidant Response ◽  
Autism Spectrum ◽  
Metal Exposure ◽  
Gulf War Syndrome ◽  
Guillain Barré ◽  
Lateral Sclerosis

Metals play important roles in the human body, maintaining cell structure and regulating gene expression, neurotransmission, and antioxidant response, to name a few. However, excessive metal accumulation in the nervous system may be toxic, inducing oxidative stress, disrupting mitochondrial function, and impairing the activity of numerous enzymes. Damage caused by metal accumulation may result in permanent injuries, including severe neurological disorders. Epidemiological and clinical studies have shown a strong correlation between aberrant metal exposure and a number of neurological diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, autism spectrum disorders, Guillain–Barré disease, Gulf War syndrome, Huntington’s disease, multiple sclerosis, Parkinson’s disease, and Wilson’s disease. Here, we briefly survey the literature relating to the role of metals in neurodegeneration.

scholarly journals Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation

2020 ◽  
Vol 21 (9) ◽  
pp. 3219 ◽  
Author(s):  
Andrea Crespo-Castrillo ◽  
Maria-Angeles Arevalo
Keyword(s):  
Neurological Diseases ◽  
Autism Spectrum ◽  
Sexual Differences ◽  
Main Role ◽  
Cell Functions ◽  
Physiological Processes ◽  
Males And Females ◽  
The Brain ◽  
Lateral Sclerosis

There are sexual differences in the onset, prevalence, and outcome of numerous neurological diseases. Thus, in Alzheimer’s disease, multiple sclerosis, and major depression disorder, the incidence in women is higher than in men. In contrast, men are more likely to present other pathologies, such as amyotrophic lateral sclerosis, Parkinson’s disease, and autism spectrum. Although the neurological contribution to these diseases has classically always been studied, the truth is that neurons are not the only cells to be affected, and there are other cells, such as glial cells, that are also involved and could be key to understanding the development of these pathologies. Sexual differences exist not only in pathology but also in physiological processes, which shows how cells are differentially regulated in males and females. One of the reasons these sexual differences may occur could be due to the different action of sex hormones. Many studies have shown an increase in aromatase levels in the brain, which could indicate the main role of estrogens in modulating proinflammatory processes. This review will highlight data about sex differences in glial physiology and how estrogenic compounds, such as estradiol and tibolone, could be used as treatment in neurological diseases due to their anti-inflammatory effects and the ability to modulate glial cell functions.

scholarly journals An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9592
Author(s):  
Emilia Zgorzynska ◽  
Barbara Dziedzic ◽  
Anna Walczewska
Keyword(s):  
Leucine Zipper ◽  
Target Genes ◽  
Protective Efficacy ◽  
Antioxidant Response ◽  
Activation Mechanism ◽  
Age Related ◽  
Nrf2 Activation ◽  
Metabolic Conditions ◽  
Lateral Sclerosis

Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.

scholarly journals An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 216 ◽  
Author(s):  
Marika Cordaro ◽  
Salvatore Cuzzocrea ◽  
Rosalia Crupi
Keyword(s):  
Nervous System ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Monocytes And Macrophages ◽  
Central Nervous Systems ◽  
The Central Nervous System ◽  
Spectrum Disorders ◽  
Dynamic Series ◽  
Preclinical And Clinical Studies

The inflammation process represents of a dynamic series of phenomena that manifest themselves with an intense vascular reaction. Neuroinflammation is a reply from the central nervous system (CNS) and the peripheral nervous system (PNS) to a changed homeostasis. There are two cell systems that mediate this process: the glia of the CNS and the lymphocites, monocytes, and macrophages of the hematopoietic system. In both the peripheral and central nervous systems, neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, and in neuropsychiatric illnesses, such as depression and autism spectrum disorders. The resolution of neuroinflammation is a process that allows for inflamed tissues to return to homeostasis. In this process the important players are represented by lipid mediators. Among the naturally occurring lipid signaling molecules, a prominent role is played by the N-acylethanolamines, namely N-arachidonoylethanolamine and its congener N-palmitoylethanolamine, which is also named palmitoylethanolamide or PEA. PEA possesses a powerful neuroprotective and anti-inflammatory power but has no antioxidant effects per se. For this reason, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treating neuroinflammation. The aim of this review is to discuss the role of ultramicronized PEA and co-ultramicronized PEA with luteolin in several neurological diseases using preclinical and clinical approaches.

scholarly journals Medial prefrontal cortex in neurological diseases

2019 ◽  
Vol 51 (9) ◽  
pp. 432-442 ◽  
Author(s):  
Pan Xu ◽  
Ai Chen ◽  
Yipeng Li ◽  
Xuezhi Xing ◽  
Hui Lu
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Cognitive Process ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Cortical Region ◽  
Spectrum Disorders ◽  
Preclinical And Clinical Studies ◽  
Regulation Of Emotion

The medial prefrontal cortex (mPFC) is a crucial cortical region that integrates information from numerous cortical and subcortical areas and converges updated information to output structures. It plays essential roles in the cognitive process, regulation of emotion, motivation, and sociability. Dysfunction of the mPFC has been found in various neurological and psychiatric disorders, such as depression, anxiety disorders, schizophrenia, autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, and addiction. In the present review, we summarize the preclinical and clinical studies to illustrate the role of the mPFC in these neurological diseases.

The Role of Inflammation in Neurological Disorders

2018 ◽  
Vol 24 (14) ◽  
pp. 1485-1501 ◽  
Author(s):  
Diana Degan ◽  
Raffaele Ornello ◽  
Cindy Tiseo ◽  
Antonio Carolei ◽  
Simona Sacco ◽  
...  
Keyword(s):  
Brain Injuries ◽  
Wide Spectrum ◽  
Neurological Diseases ◽  
Myelin Proteins ◽  
Immune Mediated ◽  
Inflammatory Processes ◽  
History Of ◽  
Neurological Conditions ◽  
Lateral Sclerosis

Traditionally neurological diseases have been classified, on the basis of their pathogenesis, into vascular, degenerative, inflammatory and traumatic diseases. Examples of the main inflammatory neurological diseases include multiple sclerosis, which is characterized by an immune-mediated response against myelin proteins, and meningoencephalitis, where the inflammatory response is triggered by infectious agents. However, recent evidence suggests a potential role of inflammatory mechanisms also in neurological conditions not usually categorized as inflammatory, such as Alzheimer’s disease, Parkinson’s disease, Huntington’ disease, amyotrophic lateral sclerosis, stroke and traumatic brain injuries. The activation of glial cells and of complement-mediated pathways, the synthesis of inflammation mediators, and the recruitment of leukocytes are the key elements of secondary inflammatory injury following a wide spectrum of primary brain injuries. A better understanding of the role that inflammatory processes play in the natural history of diseases is essential in order to identify potential therapeutic targets and to develop integrated pharmacological approaches acting at different levels and stages of the diseases.

Metals and neurodegeneration

2020 ◽  
pp. 417-424
Author(s):  
Susan Peters ◽  
Anne E Visser ◽  
Marc Weisskopf ◽  
Marianthi-Anna Kioumourtzoglou ◽  
Roel Vermeulen
Keyword(s):  
Neurodegenerative Disorders ◽  
Epidemiological Studies ◽  
Metal Exposure ◽  
Reverse Causality ◽  
Long Latency ◽  
Contaminated Food ◽  
Genetic And Environmental Factors ◽  
Occupational Settings ◽  
Lateral Sclerosis

Neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are thought to be caused by both genetic and environmental factors. Several metals and metalloids have been identified as neurotoxicants and exposure may occur, for example, via air pollution, contaminated food or drinking water, cigarette smoke, or in occupational settings. Epidemiological evidence of associations between metal exposure and neurodegenerative disorders, however, is scarce. Here we provide an overview of metals that have been suggested to play a role in neurodegeneration. Investigating these associations is challenged by accurate case ascertainment due to complicated diagnosis, multifactorial disease mechanisms, long latency requiring retrospective exposure assessment, and possible reverse causality when comparing cases and controls. Further research on understanding the role of metals in the pathology of neurodegenerative disorders is needed. Future epidemiological studies should be large and high-quality studies to provide the crucial evidence on metal exposures as possible risk factors.

scholarly journals Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-27
Author(s):  
Ke Song ◽  
Yuanyuan Li ◽  
Hanlai Zhang ◽  
Na An ◽  
Yufei Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Inflammatory Responses ◽  
Small Vessel Disease ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cerebrovascular System ◽  
Lateral Sclerosis

The blood-brain barrier (BBB), as a crucial gate of brain-blood molecular exchange, is involved in the pathogenesis of multiple neurological diseases. Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the scavenger system. Since oxidative stress plays a significant role in the production and maintenance of the BBB, the cerebrovascular system is especially vulnerable to it. The pathways that initiate BBB dysfunction include, but are not limited to, mitochondrial dysfunction, excitotoxicity, iron metabolism, cytokines, pyroptosis, and necroptosis, all converging on the generation of ROS. Interestingly, ROS also provide common triggers that directly regulate BBB damage, parameters including tight junction (TJ) modifications, transporters, matrix metalloproteinase (MMP) activation, inflammatory responses, and autophagy. We will discuss the role of oxidative stress-mediated BBB disruption in neurological diseases, such as hemorrhagic stroke, ischemic stroke (IS), Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and cerebral small vessel disease (CSVD). This review will also discuss the latest clinical evidence of potential biomarkers and antioxidant drugs towards oxidative stress in neurological diseases. A deeper understanding of how oxidative stress damages BBB may open up more therapeutic options for the treatment of neurological diseases.

scholarly journals Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes

2019 ◽  
Vol 13 ◽  
Author(s):  
Juan Xiong ◽  
Shimeng Chen ◽  
Nan Pang ◽  
Xiaolu Deng ◽  
Lifen Yang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Risk Genes

scholarly journals Main role of antibodies in demyelination and axonal damage in Multiple Sclerosis

2021 ◽  
Author(s):  
Úrsula Muñoz ◽  
Cristina Sebal ◽  
Esther Escudero ◽  
Margaret Esiri ◽  
John Tzartos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
B Cells ◽  
Plasma Cells ◽  
Neurological Diseases ◽  
Axonal Damage ◽  
Main Role ◽  
Normal Appearing White Matter ◽  
Lateral Sclerosis

Abstract Background Antibodies and oxidative stress are hallmarks of multiple sclerosis (MS) lesions. We aimed to clarify the relation between them, their role in MS patients, and to investigate their specificity, comparing MS with classical neurodegenerative diseases (ND). Methods Brain samples from 14 MS cases, 6 with ND and 9 without neurological diseases (controls). Immunohistochemistry assays were used to detect oxidized lipids (EO6), IgG and IgM, oligodendrocytes (Olig2), axons (NF, neurofilament) and cellular (TUNEL) and axonal damage (APP, amyloid precursor protein). Results We did not observe EO6 in controls. All samples from MS patients showed EO6 in oligodendrocytes and axons within lesions. We did not detect co-localization between EO6 and antibodies. Neither did we between EO6 and TUNEL or APP. 94.4% of TUNEL positive cells in normal appearing white matter were also stained for IgG and 75.5% for IgM. IgM, but not IgG co-localized with APP. EO6 was associated with axonal damage in amyotrophic lateral sclerosis (ALS). We did not observe association between antibodies and cellular or axonal damage in ND patients. MS patients showed a higher number of B cells and plasma cells in the lesions and meninges than controls. The number of B cells and plasma cells was associated with the presence of antibodies and with the activity of the lesions. Conclusions We observed a main role of B-lymphocytes in the development of MS lesions. Antibodies contribute to the oligodendrocyte and axonal damage in MS. Oxidative stress was associated with axonal damage in ALS.

A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kajal Rawat ◽  
Neha Singh ◽  
Puja Kumari ◽  
Lekha Saha
Keyword(s):  
Gut Microbiota ◽  
Ketogenic Diet ◽  
Gut Microbiome ◽  
Neurological Diseases ◽  
Critical Role ◽  
Autism Spectrum ◽  
Cns Disorders ◽  
Gut Microbes

AbstractThe gut microbiota plays an important role in neurological diseases via the gut–brain axis. Many factors such as diet, antibiotic therapy, stress, metabolism, age, geography and genetics are known to play a critical role in regulating the colonization pattern of the microbiota. Recent studies have shown the role of the low carbohydrate, adequate protein, and high fat “ketogenic diet” in remodeling the composition of the gut microbiome and thereby facilitating protective effects in various central nervous system (CNS) disorders. Gut microbes are found to be involved in the pathogenesis of various CNS disorders like epilepsy, Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorders (ASDs), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and stress, anxiety and depression. In vivo studies have shown an intricate link between gut microbes and KD and specific microbes/probiotics proved useful in in vivo CNS disease models. In the present review, we discuss the gut–brain bidirectional axis and the underlying mechanism of KD-based therapy targeting gut microbiome in in vivo animal models and clinical studies in neurological diseases. Also, we tried to infer how KD by altering the microbiota composition contributes towards the protective role in various CNS disorders. This review helps to uncover the mechanisms that are utilized by the KD and gut microbiota to modulate gut–brain axis functions and may provide novel opportunities to target therapies to the gut to treat neurologic disorders.

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