Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer

2020 ◽  
Vol 16 (8) ◽  
pp. 1058-1068
Author(s):  
Faizana Fayaz ◽  
Faheem H. Pottoo ◽  
Sadat Shafi ◽  
Mushtaq A. Wani ◽  
Sharad Wakode ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Green Chemistry ◽  
Ozone Depletion ◽  
Critical Role ◽  
Chemical Substance ◽  
Standards Of Living ◽  
Improper Use ◽  
High Standards ◽  
Lateral Sclerosis

Medicinal Chemistry has played a critical role in evolving new products, resources and processes which inexorably correspond to our high standards of living. Unfortunately, this has also caused deterioration of human health and threats to the global environment, even deaths when highly exposed to certain chemicals, whether due to improper use, mishandling or disposal. There are chemicals, which apart from being carcinogens, endocrine disruptors or neurotoxins, are also responsible for climate change and ozone depletion. Certain chemicals are known to cause neurotoxicity and are having tendencies to damage the central and peripheral nervous system or brain by damaging neurons or cells which are responsible for transmitting and processing of signals. This has raised serious concerns for the use and handling of such chemicals and has given growth to a relatively new emerging field known as Green Chemistry that strives to achieve sustainability at the molecular level and has an ability to harness chemicals to meet environmental and economic goals. It has been reported in the literature that apart from family history in the aetiology of Amyotrophic lateral Sclerosis (ALS), also termed as “Lou Gehrig’s disease”, a neurological disorder, environmental factors, heavy metals, particularly selenium, lead, mercury, cadmium, formaldehyde, pesticides and certain herbicides are known to cause ALS. ALS, a progressive neurodegenerative disease affects the motor cortex, brain stem and spinal cord, causing muscular weakness, spasticity, and hyperreflexia. In this article we are aiming to discuss and summarize the various corroborations and findings supporting the undesirable role of chemical substance/herbicides/pesticides in ALS aetiology and its mitigation by adopting green chemistry.

scholarly journals Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 10 (10) ◽  
pp. 675
Author(s):  
Hyun-Jun Choi ◽  
Sun Joo Cha ◽  
Jang-Won Lee ◽  
Hyung-Jun Kim ◽  
Kiyoung Kim
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Glycogen Synthase Kinase 3 ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3β activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3β inactivation plays a neuroprotective role in ALS pathogenesis. GSK3β activity shows an increase in various ALS models and patients. Furthermore, GSK3β inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3β in ALS and provides an overview of how the dysfunction of GSK3β activity contributes to ALS pathogenesis.

The Role of Autophagy: What can be Learned from the Genetic Forms of Amyotrophic Lateral Sclerosis

2010 ◽  
Vol 9 (3) ◽  
pp. 268-278 ◽  
Author(s):  
Livia Pasquali ◽  
Riccardo Ruffoli ◽  
Federica Fulceri ◽  
Sara Pietracupa ◽  
Gabriele Siciliano ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis

scholarly journals Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-15
Author(s):  
Vasily Vorobyov ◽  
Alexander Deev ◽  
Frank Sengpiel ◽  
Vladimir Nebogatikov ◽  
Aleksey A. Ustyugov
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Beta Activity ◽  
Systemic Injection ◽  
Eeg Spectra ◽  
Electroencephalogram Eeg ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

scholarly journals Debt and Sacrifice: The Role of Scapegoats in the Economic Crises

Religions ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 128
Author(s):  
Luis Enrique Alonso ◽  
Carlos J. Fernández Rodríguez
Keyword(s):  
Financial Markets ◽  
Social Relations ◽  
Critical Role ◽  
Social Groups ◽  
Symbolic Violence ◽  
Personal Bankruptcy ◽  
Economic Relations ◽  
Modern Economy ◽  
Standards Of Living

Despite the process of secularization and modernization, in contemporary societies, the role of sacrifice is still relevant. One of the spaces where sacrifice actually performs a critical role is the realm of modern economy, particularly in the event of a financial crisis. Such crises represent situations defined by an outrageous symbolic violence in which social and economic relations experience drastic transformations, and their victims end up suffering personal bankruptcy, indebtedness, lower standards of living or poverty. Crises show the flagrant domination present in social relations: this is proven in the way crises evolve, when more and more social groups marred by a growing vulnerability are sacrificed to appease financial markets. Inspired by the theoretical framework of the French anthropologist René Girard, our intention is to explore how the hegemonic narrative about the crisis has been developed, highlighting its sacrificial aspects.

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

The epidemiology of amyotrophic lateral sclerosis in the Mount Etna region: a possible pathogenic role of volcanogenic metals

2016 ◽  
Vol 23 (5) ◽  
pp. 964-972 ◽  
Author(s):  
A. Nicoletti ◽  
R. Vasta ◽  
V. Venti ◽  
G. Mostile ◽  
S. Lo Fermo ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mount Etna ◽  
Pathogenic Role ◽  
Lateral Sclerosis

Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals

2003 ◽  
Vol 61 (4) ◽  
pp. 365-374 ◽  
Author(s):  
Maria Teresa Carrı̀ ◽  
Alberto Ferri ◽  
Mauro Cozzolino ◽  
Lilia Calabrese ◽  
Giuseppe Rotilio
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis

scholarly journals Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial)

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e015434 ◽  
Author(s):  
Eleonora Dalla Bella ◽  
Irene Tramacere ◽  
Giovanni Antonini ◽  
Giuseppe Borghero ◽  
Margherita Capasso ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Amyotrophic Lateral Sclerosis ◽  
Placebo Group ◽  
Phase Ii ◽  
Critical Role ◽  
Protein Translation ◽  
Phase Iii ◽  
Protein Accumulation ◽  
Neuroprotective Effects ◽  
Lateral Sclerosis

IntroductionRecent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumulation and endoplasmic reticulum overload. Guanabenz proved to rescue motoneurons from misfolding protein stress both in in vitro and in vivo ALS models, making it a potential disease-modifying drug in patients. It is conceivable investigating whether its neuroprotective effects based on the inhibition of eIF2α dephosphorylation can change the progression of ALS.Methods and analysesProtocolised Management In Sepsis is a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial with futility design. We will investigate clinical outcomes, safety, tolerability and biomarkers of neurodegeneration in patients with ALS treated with guanabenz or riluzole alone for 6 months. The primary aim is to test if guanabenz can reduce the proportion of patients progressed to a higher stage of disease at 6 months compared with their baseline stage as measured by the ALS Milano-Torino Staging (ALS-MITOS) system and to the placebo group. Secondary aims are safety, tolerability and change in at least one biomarker of neurodegeneration in the guanabenz arm compared with the placebo group. Findings will provide reliable data on the likelihood that guanabenz can slow the course of ALS in a phase III trial.Ethics and disseminationThe study protocol was approved by the Ethics Committee of IRCCS ‘Carlo Besta Foundation’ of Milan (Eudract no. 2014-005367-32 Pre-results) based on the Helsinki declaration.

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