scholarly journals New Promising Therapeutic Avenues of Curcumin in Brain Diseases

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 236
Author(s):  
Tarek Benameur ◽  
Giulia Giacomucci ◽  
Maria Antonietta Panaro ◽  
Melania Ruggiero ◽  
Teresa Trotta ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Curcuma Longa ◽  
Brain Diseases ◽  
Neuroprotective Effects ◽  
Parkinson’S Diseases ◽  
Brain Structure And Function ◽  
Anti Oxidant ◽  
And Function

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called “spice of life”, in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer’s Diseases, Parkinson’s Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals Neuropharmacological Effects of Quercetin: A Literature-Based Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Shahazul Islam ◽  
Cristina Quispe ◽  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Ahmed Al-Harrasi ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Animal Experiments ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Neuroprotective Effects

Quercetin (QUR) is a natural bioactive flavonoid that has been lately very studied for its beneficial properties in many pathologies. Its neuroprotective effects have been demonstrated in many in vitro studies, as well as in vivo animal experiments and human trials. QUR protects the organism against neurotoxic chemicals and also can prevent the evolution and development of neuronal injury and neurodegeneration. The present work aimed to summarize the literature about the neuroprotective effect of QUR using known database sources. Besides, this review focuses on the assessment of the potential utilization of QUR as a complementary or alternative medicine for preventing and treating neurodegenerative diseases. An up-to-date search was conducted in PubMed, Science Direct and Google Scholar for published work dealing with the neuroprotective effects of QUR against neurotoxic chemicals or in neuronal injury, and in the treatment of neurodegenerative diseases. Findings suggest that QUR possess neuropharmacological protective effects in neurodegenerative brain disorders such as Alzheimer’s disease, Amyloid β peptide, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. In summary, this review emphasizes the neuroprotective effects of QUR and its advantages in being used in complementary medicine for the prevention and treatment o of different neurodegenerative diseases.

Literature Evidence and ARRIVE Assessment on Neuroprotective Effects of Flavonols in Neurodegenerative Diseases' Models

2018 ◽  
Vol 17 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Ana Carolina Bombardi Duarte ◽  
Maycon Giovani Santana ◽  
Guilherme di Camilo Orfali ◽  
Carlos Tadeu Parisi de Oliveira ◽  
Denise Goncalves Priolli
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuroprotective Effects ◽  
Major Health Problem ◽  
Multifactorial Diseases ◽  
Research Fields ◽  
Literature Evidence ◽  
Evidence Analysis ◽  
High Concentrations

Background and Objective: This paper was based on a literature search of PubMed and Scielo databases using the keywords “Flavonoids, Neuroprotection, Quercetin, Rutin, Isoquercitrin, Alzheimer, Parkinson, Huntington” and combinations of all the words. Method: We collected relevant publications, during the period of 2000 to 2016, emphasizing in vivo and in vitro studies with neurological assessment of flavonol's potentials, as well as classifying studies according to evidence levels, in order to elucidate evidence-based literature and its application on clinical research. In addition, we highlight the importance of flavonols in modern research fields, indicating their neuroprotective potential and use thereof as preventive and therapeutic treatment of numerous neurodegenerative disease. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, represent worldwide a major health problem with great financial impact. They are multifactorial diseases, hallmarked by similar pathogenesis that covers conditions such as oxidative stress, formation of free radicals, abnormal protein dynamics (degradation and aggregation), mitochondrial dysfunction, lipid peroxidation and cellular death or senescence. Flavonols are polyphenolic compounds, widely distributed in the plant kingdom and found in high concentrations in vegetables, fruits and teas. Their neuroprotective effects are mainly related to their antioxidant, anti-proliferative and anti-inflammatory properties. Conclusion: It was this paper's intention to contribute with an evidence analysis of recent studies approaching neuroprotective effects of flavonols and the potential to conduct human clinical studies.

scholarly journals A New Treatment Strategy for Parkinson's Disease through the Gut–Brain Axis

2017 ◽  
Vol 26 (9) ◽  
pp. 1560-1571 ◽  
Author(s):  
Dong Seok Kim ◽  
Ho-Il Choi ◽  
Yun Wang ◽  
Yu Luo ◽  
Barry J. Hoffer ◽  
...  
Keyword(s):  
Risk Factor ◽  
Neurodegenerative Diseases ◽  
Physiological Role ◽  
Open Label ◽  
Effective Treatment Option ◽  
Neuroprotective Effects ◽  
Double Blind ◽  
Parkinson’S Diseases ◽  
Dipeptidyl Peptidase 4 Inhibitors

Molecular communications in the gut–brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut–brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based antidiabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut–brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase-4 inhibitors. Recently, the first open label clinical study of exenatide, a long-acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double-blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative diseases are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut–brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.

scholarly journals Functional Genomics of Axons and Synapses to Understand Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Andres Di Paolo ◽  
Joaquin Garat ◽  
Guillermo Eastman ◽  
Joaquina Farias ◽  
Federico Dajas-Bailador ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Functional Genomics ◽  
Molecular Basis ◽  
Parkinson’S Diseases ◽  
Functional Understanding ◽  
Resolution Level ◽  
And Function ◽  
Neuronal Disorders ◽  
Neuronal Compartments

Functional genomics studies through transcriptomics, translatomics and proteomics have become increasingly important tools to understand the molecular basis of biological systems in the last decade. In most cases, when these approaches are applied to the nervous system, they are centered in cell bodies or somatodendritic compartments, as these are easier to isolate and, at least in vitro, contain most of the mRNA and proteins present in all neuronal compartments. However, key functional processes and many neuronal disorders are initiated by changes occurring far away from cell bodies, particularly in axons (axopathologies) and synapses (synaptopathies). Both neuronal compartments contain specific RNAs and proteins, which are known to vary depending on their anatomical distribution, developmental stage and function, and thus form the complex network of molecular pathways required for neuron connectivity. Modifications in these components due to metabolic, environmental, and/or genetic issues could trigger or exacerbate a neuronal disease. For this reason, detailed profiling and functional understanding of the precise changes in these compartments may thus yield new insights into the still intractable molecular basis of most neuronal disorders. In the case of synaptic dysfunctions or synaptopathies, they contribute to dozens of diseases in the human brain including neurodevelopmental (i.e., autism, Down syndrome, and epilepsy) as well as neurodegenerative disorders (i.e., Alzheimer’s and Parkinson’s diseases). Histological, biochemical, cellular, and general molecular biology techniques have been key in understanding these pathologies. Now, the growing number of omics approaches can add significant extra information at a high and wide resolution level and, used effectively, can lead to novel and insightful interpretations of the biological processes at play. This review describes current approaches that use transcriptomics, translatomics and proteomic related methods to analyze the axon and presynaptic elements, focusing on the relationship that axon and synapses have with neurodegenerative diseases.

scholarly journals The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4700
Author(s):  
Stefania Schiavone ◽  
Maria Grazia Morgese ◽  
Paolo Tucci ◽  
Luigia Trabace
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Neuroprotective Effects ◽  
Central Nervous System Disorders ◽  
Parkinson’S Diseases ◽  
Cellular Apoptosis

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described.

scholarly journals Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions

2017 ◽  
Author(s):  
Sigrun Lange ◽  
Sharad Kholia ◽  
Uchini Kosgodage ◽  
Mariya Hristova ◽  
John Hardy ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Cancer Cells ◽  
Disease Progression ◽  
Cancer Progression ◽  
Cytoskeletal Proteins ◽  
Therapeutic Interventions ◽  
Neuroprotective Effects ◽  
Central Nervous System Damage

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

scholarly journals Sulforaphane as a Potential Protective Phytochemical against Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Andrea Tarozzi ◽  
Cristina Angeloni ◽  
Marco Malaguti ◽  
Fabiana Morroni ◽  
Silvana Hrelia ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Neuronal Loss ◽  
In Vivo Studies ◽  
Alternative Form ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Hydrolysis Of

A wide variety of acute and chronic neurodegenerative diseases, including ischemic/traumatic brain injury, Alzheimer’s disease, and Parkinson's disease, share common characteristics such as oxidative stress, misfolded proteins, excitotoxicity, inflammation, and neuronal loss. As no drugs are available to prevent the progression of these neurological disorders, intervention strategies using phytochemicals have been proposed as an alternative form of treatment. Among phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present inBrassicavegetables, has demonstrated neuroprotective effects in several in vitro and in vivo studies. In particular, evidence suggests that sulforaphane beneficial effects could be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway. Therefore, sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing neurodegeneration.

scholarly journals Infectivity versus Seeding in Neurodegenerative Diseases Sharing a Prion-Like Mechanism

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Natalia Fernández-Borges ◽  
Hasier Eraña ◽  
Saioa R. Elezgarai ◽  
Chafik Harrathi ◽  
Mayela Gayosso ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Infectious Agent ◽  
Infection Process ◽  
Biological Information ◽  
Misfolded Proteins ◽  
Parkinson’S Diseases

Prions are considered the best example to prove that the biological information can be transferred protein to protein through a conformational change. The term “prion-like” is used to describe molecular mechanisms that share similarities with the mammalian prion protein self-perpetuating aggregation and spreading characteristics. Since prions are presumably composed only of protein and are infectious, the more similar the mechanisms that occur in the different neurodegenerative diseases, the more these processes will resemble an infection.In vitroandin vivoexperiments carried out during the last decade in different neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's diseases (PD), and amyotrophic lateral sclerosis (ALS) have shown a convergence toward a unique mechanism of misfolded protein propagation. In spite of the term “infection” that could be used to explain the mechanism governing the diversity of the pathological processes, other concepts as “seeding” or “de novoinduction” are being used to describe thein vivopropagation and transmissibility of misfolded proteins. The current studies are demanding an extended definition of “disease-causing agents” to include those already accepted as well as other misfolded proteins. In this new scenario, “seeding” would be a type of mechanism by which an infectious agent can be transmitted but should not be used to define a whole “infection” process.

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