scholarly journals Iron and Neurodegeneration: From Cellular Homeostasis to Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Liliana Batista-Nascimento ◽  
Catarina Pimentel ◽  
Regina Andrade Menezes ◽  
Claudina Rodrigues-Pousada
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Genetic Factors ◽  
Therapeutic Strategies ◽  
Neuronal Dysfunction ◽  
Eukaryotic Organism ◽  
The Brain

Accumulation of iron (Fe) is often detected in the brains of people suffering from neurodegenerative diseases. High Fe concentrations have been consistently observed in Parkinson’s, Alzheimer’s, and Huntington’s diseases; however, it is not clear whether this Fe contributes to the progression of these diseases. Other conditions, such as Friedreich’s ataxia or neuroferritinopathy are associated with genetic factors that cause Fe misregulation. Consequently, excessive intracellular Fe increases oxidative stress, which leads to neuronal dysfunction and death. The characterization of the mechanisms involved in the misregulation of Fe in the brain is crucial to understand the pathology of the neurodegenerative disorders and develop new therapeutic strategies.Saccharomyces cerevisiae, as the best understood eukaryotic organism, has already begun to play a role in the neurological disorders; thus it could perhaps become a valuable tool also to study the metalloneurobiology.

scholarly journals Iron and Mechanisms of Neurotoxicity

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Gabriela A. Salvador ◽  
Romina M. Uranga ◽  
Norma M. Giusto
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Neuronal Dysfunction ◽  
Protective Mechanisms ◽  
Copper Zinc ◽  
Final Response ◽  
The Brain ◽  
Oxidative Insult

The accumulation of transition metals (e.g., copper, zinc, and iron) and the dysregulation of their metabolism are a hallmark in the pathogenesis of several neurodegenerative diseases. This paper will be focused on the mechanism of neurotoxicity mediated by iron. This metal progressively accumulates in the brain both during normal aging and neurodegenerative processes. High iron concentrations in the brain have been consistently observed in Alzheimer's (AD) and Parkinson's (PD) diseases. In this connection, metalloneurobiology has become extremely important in establishing the role of iron in the onset and progression of neurodegenerative diseases. Neurons have developed several protective mechanisms against oxidative stress, among them, the activation of cellular signaling pathways. The final response will depend on the identity, intensity, and persistence of the oxidative insult. The characterization of the mechanisms mediating the effects of iron-induced increase in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders.

scholarly journals A Review on Epilepsy and its Management

2020 ◽  
Vol 10 (3) ◽  
pp. 273-279
Author(s):  
V.V. Potnis ◽  
Ketan G. Albhar ◽  
Pritamsinh Arjun Nanaware ◽  
Vishal S. Pote
Keyword(s):  
Developing Countries ◽  
Neurological Disorders ◽  
Genetic Factors ◽  
Future Trends ◽  
Brain Infection ◽  
The World ◽  
Different Types ◽  
Patients With Epilepsy ◽  
The Brain

Today, people face various types of stress in everyday fast life and most people in the world suffer from various neurological disorder. Epilepsy is one of the most common neurological disorders of the brain, affecting about 50 million people around the world, and 90% of them are coming from developing countries. Genetic factors and brain infection, stroke, tumors and epilepsy cause high fever. It imposes a great economic burden on the health systems of countries associated with stigma and discrimination against the patient and also his family in the community, in the workplace, school and home. Many patients with epilepsy suffer from severe emotional stress, behavioral disorders and extreme social isolation. There are many different types of seizure and mechanisms by which the brain generates seizures. The two features of generating seizures are hyperexcitability of neurons and a hyper synchronousneural circuits. A variety of mechanisms alters the balance between excitation and inhibition in predisposing brain local or generalized hyperexcitability region and a hypersynchronia. Purpose of the review is to discuss the history, epidemiology, etiology, pathophysiology, classification of epilepsy, symtomps, diagnosis, management of epilepsy and future trends. Keywords: Anti-epileptic drugs, pathophysiology, seizures, epidemiology, hypersynchrony

scholarly journals RCAN1 Regulates Mitochondrial Function and Increases Susceptibility to Oxidative Stress in Mammalian Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Heshan Peiris ◽  
Daphne Dubach ◽  
Claire F. Jessup ◽  
Petra Unterweger ◽  
Ravinarayan Raghupathi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Neurodegenerative Disorders ◽  
Mammalian Cells ◽  
Cell Function ◽  
Cellular Energy ◽  
Mitochondrial Ros ◽  
Ros Accumulation ◽  
The Brain ◽  
Increased Susceptibility

Mitochondria are the primary site of cellular energy generation and reactive oxygen species (ROS) accumulation. Elevated ROS levels are detrimental to normal cell function and have been linked to the pathogenesis of neurodegenerative disorders such as Down's syndrome (DS) and Alzheimer’s disease (AD). RCAN1 is abundantly expressed in the brain and overexpressed in brain of DS and AD patients. Data from nonmammalian species indicates that increased RCAN1 expression results in altered mitochondrial function and that RCAN1 may itself regulate neuronal ROS production. In this study, we have utilized mice overexpressing RCAN1RCAN1oxand demonstrate an increased susceptibility of neurons from these mice to oxidative stress. Mitochondria from these mice are more numerous and smaller, indicative of mitochondrial dysfunction, and mitochondrial membrane potential is altered under conditions of oxidative stress. We also generated a PC12 cell line overexpressing RCAN1PC12RCAN1. Similar toRCAN1oxneurons,PC12RCAN1cells have an increased susceptibility to oxidative stress and produce more mitochondrial ROS. This study demonstrates that increasing RCAN1 expression alters mitochondrial function and increases the susceptibility of neurons to oxidative stress in mammalian cells. These findings further contribute to our understanding of RCAN1 and its potential role in the pathogenesis of neurodegenerative disorders such as AD and DS.

Role of Vitamins in Neurodegenerative Diseases: A Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Ravi Ranjan Kumar ◽  
Lovekesh Singh ◽  
Amandeep Thakur ◽  
Shamsher Singh ◽  
Bhupinder Kumar
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Vitamin D ◽  
Vitamin C ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Vitamin D Deficiency ◽  
Neurological Disorders ◽  
The Brain

Background: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin-B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin-D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, Vitamin-C and Vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. Vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

scholarly journals The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2640 ◽  
Author(s):  
Fakhri ◽  
Aneva ◽  
Farzaei ◽  
Sobarzo-Sánchez
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Spinal Cord Injuries ◽  
Neurological Diseases ◽  
Mechanisms Of Action ◽  
Clinical Perspective ◽  
Neuroprotective Effects ◽  
Brain And Spinal Cord ◽  
Neuronal Disorders

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.

scholarly journals Tissue-Specificity of Antibodies Raised Against TrkB and p75NTR Receptors; Implications for Platelets as Models of Neurodegenerative Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Samuel Fleury ◽  
Imane Boukhatem ◽  
Jessica Le Blanc ◽  
Mélanie Welman ◽  
Marie Lordkipanidzé
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Blood Circulation ◽  
Tissue Specificity ◽  
Receptor Kinase ◽  
Calcium Dependent ◽  
Neuronal Growth Factor ◽  
The Central Nervous System ◽  
The Brain

Platelets and neurons share many similarities including comparable secretory granule types with homologous calcium-dependent secretory mechanisms as well as internalization, sequestration and secretion of many neurotransmitters. Thus, platelets present a high potential to be used as peripheral biomarkers to reflect neuronal pathologies. The brain-derived neurotrophic factor (BDNF) acts as a neuronal growth factor involved in learning and memory through the binding of two receptors, the tropomyosin receptor kinase B (TrkB) and the 75 kDa pan-neurotrophic receptor (p75NTR). In addition to its expression in the central nervous system, BDNF is found in much greater quantities in blood circulation, where it is largely stored within platelets. Levels 100- to 1,000-fold those of neurons make platelets the most important peripheral reservoir of BDNF. This led us to hypothesize that platelets would express canonical BDNF receptors, i.e., TrkB and p75NTR, and that the receptors on platelets would bear significant resemblance to the ones found in the brain. However, herein we report discrepancies regarding detection of these receptors using antibody-based assays, with antibodies displaying important tissue-specificity. The currently available antibodies raised against TrkB and p75NTR should therefore be used with caution to study platelets as models for neurological disorders. Rigorous characterization of antibodies and bioassays appears critical to understand the interplay between platelet and neuronal biology of BDNF.

scholarly journals POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

2021 ◽  
pp. 125-136
Author(s):  
S. A. Tsiumpala ◽  
K. M. Starchevska ◽  
V. I. Lushchak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Old Age ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
The Body ◽  
Biologically Active ◽  
Inflammatory Processes ◽  
The Brain ◽  
Potential Use

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

scholarly journals Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiuqi Chen ◽  
Wenmei Lu ◽  
Danhong Wu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rapid Growth ◽  
Nicotinamide Adenine Dinucleotide ◽  
Neurological Disorders ◽  
Potential Role ◽  
Therapeutic Strategies ◽  
Nicotinamide Adenine ◽  
The Central Nervous System ◽  
The Brain

As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) is predominantly found in the cytoplasm of cells in the central nervous system (CNS), suggesting its potential role in neurological disorders. Though SIRT2 is generally acknowledged to accelerate the development of neurological pathologies, it protects the brain from deterioration in certain circumstances. This review summarized the complex roles SIRT2 plays in the pathophysiology of diverse neurological disorders, compared and analyzed the discrete roles of SIRT2 in different conditions, and provided possible explanations for its paradoxical functions. In the future, the rapid growth in SIRT2 research may clarify its impacts on neurological disorders and develop therapeutic strategies targeting this protein.

Lysosomes and Brain Health

2018 ◽  
Vol 41 (1) ◽  
pp. 255-276 ◽  
Author(s):  
Jaiprakash Sharma ◽  
Alberto di Ronza ◽  
Parisa Lotfi ◽  
Marco Sardiello
Keyword(s):  
Neuronal Plasticity ◽  
Therapeutic Strategies ◽  
Brain Health ◽  
Developmental Needs ◽  
Fundamental Properties ◽  
System A ◽  
Lysosomal System ◽  
And Function ◽  
The Brain

One of the fundamental properties of the cell is the capability to digest and remodel its own components according to metabolic and developmental needs. This is accomplished via the autophagy-lysosome system, a pathway of critical importance in the brain, where it contributes to neuronal plasticity and must protect nonreplaceable neurons from the potentially harmful accumulation of cellular waste. The study of lysosomal biogenesis and function in the context of common and rare neurodegenerative diseases has revealed that a dysfunctional autophagy-lysosome system is the shared nexus where multiple, interconnected pathogenic events take place. The characterization of pathways and mechanisms regulating the lysosomal system and autophagic clearance offers unprecedented opportunities for the development of polyvalent therapeutic strategies based on the enhancement of the autophagy-lysosome pathway to maintain cellular homeostasis and achieve neuroprotection.

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