Protein misfolding in neurodegenerative diseases: implications and strategies

Translational Neurodegeneration, Journal Year: 2017, Volume and Issue: 6(1)

Published: March 13, 2017

A hallmark of neurodegenerative proteinopathies is the formation misfolded protein aggregates that cause cellular toxicity and contribute to proteostatic collapse. Therapeutic options are currently being explored target different steps in production processing proteins implicated disease, including synthesis, chaperone-assisted folding trafficking, degradation via proteasome autophagy pathways. Other therapies, like mTOR inhibitors activators heat shock response, can rebalance entire network. However, there major challenges impact development novel incomplete knowledge druggable disease targets their mechanism action as well a lack biomarkers monitor progression therapeutic response. notable creation collaborative ecosystems include patients, clinicians, basic translational researchers, foundations regulatory agencies promote scientific rigor clinical data accelerate therapies prevent, reverse or delay proteinopathies.

Language: Английский

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Ageing, age-related diseases and oxidative stress: What to do next?

Ageing Research Reviews, Journal Year: 2019, Volume and Issue: 57, P. 100982 - 100982

Published: Nov. 13, 2019

Language: Английский

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Involvement of Astrocytes in Alzheimer’s Disease from a Neuroinflammatory and Oxidative Stress Perspective

Frontiers in Molecular Neuroscience, Journal Year: 2017, Volume and Issue: 10

Published: Dec. 19, 2017

Alzheimer disease (AD) is a frequent and devastating neurodegenerative in humans, but still no curative treatment has been developed. Although many explicative theories have proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes brain homeostasis they become interesting targets for study AD. Changes astrocyte function observed brains from individuals with AD, as well AD vitro vivo animal models. The presence amyloid beta (Aβ) shown disrupt gliotransmission, neurotransmitter uptake, alter calcium signaling astrocytes. Furthermore, express apolipoprotein E involved production, degradation removal Aβ. As well, changes that precede other pathological characteristics point an early contribution astroglia this disease. Astrocytes participate inflammatory/immune responses central nervous system. Aβ activates different cell receptors intracellular pathways, mainly advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) pathway, responsible transcription pro-inflammatory cytokines chemokines release these agents may induce cellular damage or even stimulate production Additionally, induces appearance oxidative stress (OS) reactive oxygen species nitrogen astrocytes, affecting among others, levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing risk excitotoxicity) mitochondrial function. Excessive neuroinflammation OS seem be both. Aβ/NF-κB interaction play role inflammatory present In paper, we also discuss therapeutic measures highlighting pathology. Several new approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids natural phytochemicals explored obtaining some promising results regarding cognitive improvements attenuation neuroinflammation. Novel strategies comprising aimed reduce proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, various antioxidatives such resveratrol, tocotrienol, anthocyanins, epicatechin, showing beneficial effects

Language: Английский

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Neuroprotective Effect of Antioxidants in the Brain

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(19), P. 7152 - 7152

Published: Sept. 28, 2020

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility neuronal damage functional deficits, via changes in the neurodegenerative diseases. Overabundance abnormal levels ROS and/or overload metals are regulated by cellular defense mechanisms, intracellular signaling, physiological functions antioxidants brain. Single complex compounds targeting stress, redox metals, cell death have been evaluated multiple preclinical clinical trials as a complementary therapeutic strategy for combating stress associated with Herein, we present general analysis overview various suggest potential courses treatments neuroprotection from injury. This review focuses on enzymatic non-enzymatic mechanisms examines relative advantages methodological concerns when assessing treatment disorders.

Language: Английский

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On Cell Loss and Selective Vulnerability of Neuronal Populations in Parkinson's Disease

Frontiers in Neurology, Journal Year: 2018, Volume and Issue: 9

Published: June 19, 2018

Significant advances have been made uncovering the factors that render neurons vulnerable in Parkinson's disease (PD). However, critical pathogenic events leading to cell loss remain poorly understood, complicating development of disease-modifying interventions. Given cardinal motor symptoms and pathology PD involve dopamine (DA) substantia nigra pars compacta (SNc), a majority work field has focused on this specific neuronal population. however, is not DA exclusively: pathology, most notably form Lewy bodies neurites, reported multiple regions central peripheral nervous system, including for example locus coeruleus, dorsal raphe nucleus vagus. Cell and/or terminal these additional nuclei likely contribute some other and, non-motor features. exactly what show actual, well-documented, presently unclear. In review we will first examine strength evidence describing idiopathic PD, as well order which occurs. Secondly, discuss neurochemical, morphological physiological characteristics SNc vulnerable, being shared across PD-affected populations. Some insights raised by focusing underpinnings selective vulnerability might be helpful facilitate new strategies improve animal models disease.

Language: Английский

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Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(1)

Published: June 11, 2018

Abstract Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition enzymatic defense mechanisms, there are compounds (usually referred as antioxidants) that offer protection against oxidative events. Among them, melatonin its metabolites constitute particularly efficient family. They OS individual entities through wide variety mechanisms electron transfer, hydrogen radical adduct formation, metal chelation, by repairing biological targets. fact, many them can be classified multipurpose antioxidants. However, what seems unique melatonin's family is their collective effects. Because members metabolically related, most expected present living organisms wherever produced. Therefore, exerted may viewed result combined antioxidant effects parent molecule metabolites. Melatonin's rather exceptional regard, offering versatile OS. It certainly one best nature's defenses damage.

Language: Английский

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Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(2), P. 94 - 108

Published: Jan. 14, 2019

Language: Английский

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Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 18(10), P. 595 - 609

Published: Aug. 9, 2017

Language: Английский

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Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review

Neuroscience, Journal Year: 2019, Volume and Issue: 406, P. 1 - 21

Published: Feb. 28, 2019

Language: Английский

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Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 4, 2020

Centella asiatica (also known as (L.) Urb. or Gotu kola) is a traditional Chinese medicine with extensive medicinal value, which mainly used in Southeast Asian countries. This study aimed to summarize the effects of C. and its main components on neurological diseases, endocrine skin cardiovascular gastrointestinal immune gynecological well potential molecular mechanisms, pathological mechanism these diseases based changes at level. The results showed that triterpenoids had beneficial were confirmed through clinical studies. They exhibited anti-inflammatory, anti-oxidative stress, anti-apoptotic effects, improvement mitochondrial function. However, further studies are urgently required due low level evidence lack patients.

Language: Английский

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