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 Modulation of Glial Function in Health, Aging, and Neurodegenerative Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Kendra L. Hanslik ◽  
Kaitlyn M. Marino ◽  
Tyler K. Ulland
Keyword(s):  
Synaptic Plasticity ◽  
Immune Cells ◽  
Neurodegenerative Disorders ◽  
Ion Homeostasis ◽  
Neuronal Dysfunction ◽  
Health Aging ◽  
Glial Function ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system (CNS), glial cells, such as microglia and astrocytes, are normally associated with support roles including contributions to energy metabolism, synaptic plasticity, and ion homeostasis. In addition to providing support for neurons, microglia and astrocytes function as the resident immune cells in the brain. The glial function is impacted by multiple aspects including aging and local CNS changes caused by neurodegeneration. During aging, microglia and astrocytes display alterations in their homeostatic functions. For example, aged microglia and astrocytes exhibit impairments in the lysosome and mitochondrial function as well as in their regulation of synaptic plasticity. Recent evidence suggests that glia can also alter the pathology associated with many neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Shifts in the microbiome can impact glial function as well. Disruptions in the microbiome can lead to aberrant microglial and astrocytic reactivity, which can contribute to an exacerbation of disease and neuronal dysfunction. In this review, we will discuss the normal physiological functions of microglia and astrocytes, summarize novel findings highlighting the role of glia in aging and neurodegenerative diseases, and examine the contribution of microglia and astrocytes to disease progression.

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 Diagnostic and Therapeutic Potential of Exosomes in Neurodegenerative Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Panyue Gao ◽  
Xinrong Li ◽  
Xinzhe Du ◽  
Sha Liu ◽  
Yong Xu
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Brain Function ◽  
Genetic Information ◽  
Therapeutic Potential ◽  
Early Biomarkers ◽  
Drug Molecules ◽  
The Brain ◽  
Lateral Sclerosis

Neurodegenerative diseases are closely related to brain function and the progression of the diseases are irreversible. Due to brain tissue being not easy to acquire, the study of the pathophysiology of neurodegenerative disorders has many limitations—lack of reliable early biomarkers and personalized treatment. At the same time, the blood-brain barrier (BBB) limits most of the drug molecules into the damaged areas of the brain, which makes a big drop in the effect of drug treatment. Exosomes, a kind of endogenous nanoscale vesicles, play a key role in cell signaling through the transmission of genetic information and proteins between cells. Because of the ability to cross the BBB, exosomes are expected to link peripheral changes to central nervous system (CNS) events as potential biomarkers, and can even be used as a therapeutic carrier to deliver molecules specifically to CNS. Here we summarize the role of exosomes in pathophysiology, diagnosis, prognosis, and treatment of some neurodegenerative diseases (Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis).

Glia in the pathogenesis of neurodegenerative diseases

2014 ◽  
Vol 42 (5) ◽  
pp. 1291-1301 ◽  
Author(s):  
Alexei Verkhratsky ◽  
Vladimir Parpura ◽  
Marcela Pekna ◽  
Milos Pekny ◽  
Michael Sofroniew
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Contemporary View ◽  
Novel Targets ◽  
The Brain ◽  
Prevention And Therapy

Exclusively neuron-centric approaches to neuropathological mechanisms have not resulted in major new breakthroughs in the prevention and therapy of neurodegenerative diseases. In the present paper, we review the role of glia in neurodegeneration in an attempt to identify novel targets that could be used to develop much-needed strategies for the containment and cure of neurodegenerative disorders. We discuss this in the context of glial roles in the homoeostasis and defence of the brain. We consider the mounting evidence supporting a change away from the perception of reactive glial responses merely as secondary detrimental processes that exacerbate the course of neurological disorders, in favour of an emerging contemporary view of glial pathological responses as complex and multistaged defensive processes that also have the potential for dysfunction.

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

2019 ◽  
Vol 18 (8) ◽  
pp. 581-597 ◽  
Author(s):  
Ambreen Fatima ◽  
Yasir Hasan Siddique
Keyword(s):  
Medicinal Plants ◽  
Mechanism Of Action ◽  
Neurodegenerative Disorders ◽  
Treatment Strategies ◽  
Dietary Supplementation ◽  
Plant Polyphenols ◽  
Promising Candidate ◽  
Naturally Occurring ◽  
The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

scholarly journals The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

2018 ◽  
Vol 7 (11) ◽  
pp. 461 ◽  
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Glucose Dysregulation ◽  
Near Future ◽  
The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

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.

Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders

2021 ◽  
Vol 478 (14) ◽  
pp. 2733-2758
Author(s):  
Aaron T. Balana ◽  
Matthew R. Pratt
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Posttranslational Modification ◽  
Protein Quality ◽  
Neuronal Dysfunction ◽  
Neuronal Communication ◽  
Programmed Death ◽  
Growing Body ◽  
Potential Strategy ◽  
Therapeutic Avenue

Neurodegenerative diseases such as Alzheimer's and Parkinson's remain highly prevalent and incurable disorders. A major challenge in fully understanding and combating the progression of these diseases is the complexity of the network of processes that lead to progressive neuronal dysfunction and death. An ideal therapeutic avenue is conceivably one that could address many if not all of these multiple misregulated mechanisms. Over the years, chemical intervention for the up-regulation of the endogenous posttranslational modification (PTM) O-GlcNAc has been proposed as a potential strategy to slow down the progression of neurodegeneration. Through the development and application of tools that allow dissection of the mechanistic roles of this PTM, there is now a growing body of evidence that O-GlcNAc influences a variety of important neurodegeneration-pertinent mechanisms, with an overall protective effect. As a PTM that is appended onto numerous proteins that participate in protein quality control and homeostasis, metabolism, bioenergetics, neuronal communication, inflammation, and programmed death, O-GlcNAc has demonstrated beneficence in animal models of neurodegenerative diseases, and its up-regulation is now being pursued in multiple clinical studies.

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