Smouldering Lesion in MS: Microglia, Lymphocytes and Pathobiochemical Mechanisms DOI Open Access
Dániel Pukoli, László Vécsei

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12631 - 12631

Published: Aug. 10, 2023

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Immune cell infiltration can lead to permanent activation macrophages microglia in parenchyma, resulting demyelination neurodegeneration. Thus, neurodegeneration that begins with acute lymphocytic inflammation may progress inflammation. This thought underlie development so-called smouldering lesions. These lesions evolve from inflammatory are associated continuous low-grade over many years. Their presence poor prognosis promotes transition progressive MS, which later manifest clinically as MS when exceeds upper limit functional compensation. In lesions, only moderate activity, a toxic environment clearly identifiable contributes degeneration neurons, axons, oligodendrocytes and, thus, clinical progression. addition cells immune system, oxidative stress mitochondrial damage, hypoxia caused by energy deficit iron accumulation play role this process. classical mediators, contains high concentrations oxidants ions, well excitatory neurotransmitter glutamate. review, we will discuss how these pathobiochemical markers mechanisms, alone or combination, neuronal, axonal, glial death ultimately process neuroinflammation neurodegeneration, then concepts conclusions emerge findings. Understanding would be important gain better insight into relationship between classification pathomechanism MS.

Language: Английский

The role of zinc, copper, manganese and iron in neurodegenerative diseases DOI

Leda Mezzaroba,

Daniela Frizon Alfieri, Andréa Name Colado Simão

et al.

NeuroToxicology, Journal Year: 2019, Volume and Issue: 74, P. 230 - 241

Published: Aug. 1, 2019

Language: Английский

Citations

417
Heavy Metals and Human Health: Possible Exposure Pathways and the Competition for Protein Binding Sites DOI Creative Commons
Danuta Witkowska, Joanna Słowik, Karolina Chilicka

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(19), P. 6060 - 6060

Published: Oct. 7, 2021

Heavy metals enter the human body through gastrointestinal tract, skin, or via inhalation. Toxic have proven to be a major threat health, mostly because of their ability cause membrane and DNA damage, perturb protein function enzyme activity. These disturb native proteins’ functions by binding free thiols other functional groups, catalyzing oxidation amino acid side chains, perturbing folding, and/or displacing essential metal ions in enzymes. The review shows physiological biochemical effects selected toxic interactions with proteins As environmental contamination heavy is one most significant global problems, some detoxification strategies are also mentioned.

Language: Английский

Citations

373
Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications DOI Open Access
Grażyna Gromadzka, Beata Tarnacka,

Anna Flaga

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(23), P. 9259 - 9259

Published: Dec. 4, 2020

Copper is one of the most abundant basic transition metals in human body. It takes part oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining integrity blood vessels, as well iron homeostasis, antioxidant defense, neurotransmitter synthesis. may also be involved cell signaling participate modulation membrane receptor-ligand interactions, control kinase related phosphatase functions, many cellular pathways. Its role important controlling gene expression nucleus. In nervous system particular, copper myelination, by modulating synaptic activity excitotoxic death cascades induced neurotrophic factors, for various neuronal functions. Current data suggest that both excess levels deficiency can harmful, careful homeostatic important. This knowledge opens up an new area potential therapeutic interventions based on supplementation or removal neurodegenerative diseases including Wilson’s disease (WD), Menkes (MD), Alzheimer’s (AD), Parkinson’s (PD), others. However, much remains to discovered, how regulate homeostasis prevent neurodegeneration, when chelate copper, supplement it.

Language: Английский

Citations

240
Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection DOI Creative Commons

Shruti Shandilya,

Sandeep Kumar, Niraj Kumar Jha

et al.

Journal of Advanced Research, Journal Year: 2021, Volume and Issue: 38, P. 223 - 244

Published: Sept. 17, 2021

Recent research on the implications of gut microbiota brain functions has helped to gather important information relationship between them. Pathogenesis neurological disorders is found be associated with dysregulation gut-brain axis. Some bacteria metabolites are directly increase in reactive oxygen species levels, one most risk factors neurodegeneration. Besides their morbid association, also play a significant role reducing onset these life-threatening disorders.Studies done recent past raises two link and brain: "gut microbiota-oxidative stress-neurodegeneration" microbiota-antioxidant-neuroprotection. This review aims gives deep insight our readers, collective studies done, focusing mediated oxidative stress involved neurodegeneration along focus those showing involvement neuroprotection.This focused three main key concepts. Firstly, mounting evidences from clinical preclinical arenas shows influence resulting dysfunctional processes. Therefore, we describe potential influencing vulnerability stress, budding causative Alzheimer's Parkinson's disease. Secondly, contributing roles been observed attenuating inflammation via its own or by producing secondary and, modulation population antioxidative anti-inflammatory probiotics have shown promising neuro resilience. Thirdly, high throughput silico tools databases correlation microbiome, health, thus providing fascinating perspective new avenues for therapeutic options.

Language: Английский

Citations

194
NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration DOI Creative Commons
Maria Quiles del Rey, Joseph D. Mancias

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: March 14, 2019

NCOA4 (Nuclear receptor coactivator 4) mediates the selective autophagic degradation of ferritin, cellular cytosolic iron storage complex, thereby playing a critical role in intracellular and systemic homeostasis. Disruptions homeostasis autophagy are observed several neurodegenerative disorders raising possibility that NCOA4-mediated ferritinophagy links these two observations may underlie, part, pathophysiology neurodegeneration. Here, we review available evidence detailing molecular mechanisms recent studies examining its erythropoiesis. We propose additional to examine potential brain context diseases.

Language: Английский

Citations

185
Cadmium and Lead Exposure, Nephrotoxicity, and Mortality DOI Creative Commons

Soisungwan Satarug,

Glenda C. Gobé, David A. Vesey

et al.

Toxics, Journal Year: 2020, Volume and Issue: 8(4), P. 86 - 86

Published: Oct. 13, 2020

The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) which most populations are exposed. Epidemiological studies examining adverse effects coexposure Cd Pb have shown that may enhance nephrotoxicity vice versa. Herein, existing tolerable intake discussed together conventional urinary threshold limit 5.24 μg/g creatinine. Dietary sources reported for average consumers in U.S., Spain, Korea, Germany China summarized. utility urine, whole blood, plasma/serum, erythrocytes quantify exposure discussed. linked one these measurements chronic kidney disease (CKD) mortality from common ailments reviewed. A level 23.2 μg/day, is less than half safe stated by guidelines, increase risk CKD 73%, one-tenth limit, defined excessive ß2-microglobulin excretion, were increased CKD, heart disease, cancer any site Alzheimer’s disease. These findings indicate current do not adequate protection. Any excretion probably indicative tubular injury. In light evolving realization interaction between Pb, actions minimize toxic metals imperative.

Language: Английский

Citations

173
Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases DOI Creative Commons
Ke Song, Yuanyuan Li,

Hanlai Zhang

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 27

Published: July 3, 2020

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

Language: Английский

Citations

142
Metals associated neurodegeneration in Parkinson’s disease: Insight to physiological, pathological mechanisms and management DOI

Khadga Raj,

Pawandeep Kaur,

Ghanshyam Das Gupta

et al.

Neuroscience Letters, Journal Year: 2021, Volume and Issue: 753, P. 135873 - 135873

Published: April 2, 2021

Language: Английский

Citations

121
Nanoparticle-mediated bioremediation as a powerful weapon in the removal of environmental pollutants DOI
Parul Chaudhary, Lukman Ahamad, Anuj Chaudhary

et al.

Journal of environmental chemical engineering, Journal Year: 2023, Volume and Issue: 11(2), P. 109591 - 109591

Published: Feb. 28, 2023

Language: Английский

Citations

113
Chemico-nanotreatment methods for the removal of persistent organic pollutants and xenobiotics in water – A review DOI
G. Karthiga Devi,

Sivasubramanian Manikandan,

Natchimuthu Karmegam

et al.

Bioresource Technology, Journal Year: 2021, Volume and Issue: 324, P. 124678 - 124678

Published: Jan. 9, 2021

Language: Английский

Citations

110