A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

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The beneficial effects of physical exercise in the brain and related pathophysiological mechanisms in neurodegenerative diseases

Laboratory Investigation ◽

10.1038/s41374-019-0232-y ◽

2019 ◽

Vol 99 (7) ◽

pp. 943-957 ◽

Cited By ~ 20

Author(s):

Yan Liu ◽

Tim Yan ◽

John Man-Tak Chu ◽

Ying Chen ◽

Sophie Dunnett ◽

...

Keyword(s):

Physical Exercise ◽

Neurodegenerative Diseases ◽

Pathophysiological Mechanisms ◽

Beneficial Effects ◽

The Brain

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Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816429115 ◽

2018 ◽

Vol 115 (52) ◽

pp. E12333-E12342 ◽

Cited By ~ 12

Author(s):

Bapurao Surnar ◽

Uttara Basu ◽

Bhabatosh Banik ◽

Anis Ahmad ◽

Brian Marples ◽

...

Keyword(s):

Oxidative Damage ◽

Neurodegenerative Diseases ◽

Neurovascular Unit ◽

Neuronal Cell ◽

Capillary Endothelium ◽

Target Cells ◽

Full Potential ◽

Beneficial Effects ◽

Neuroprotective Actions ◽

The Brain

The success of nanoparticle-mediated delivery of antioxidant and antiinflammatory-based neuroprotectants to the brain to improve neuronal functions in neurodegenerative diseases has demonstrated lesser impact instead of achieving its full potential. We hypothesized that these failures were due to a combination of parameters, such as: (i) unavailability of a delivery vehicle, which can reproducibly and efficiently transport through the brain capillary endothelium; (ii) inefficient uptake of therapeutic nanoparticles in the neuronal cell population; and (iii) limited ability of a single nanoparticle to cross the two most-impermeable biological barriers, the blood–brain barrier and mitochondrial double membrane, so that a nanoparticle can travel through the brain endothelial barrier to the mitochondria of target cells where oxidative damage is localized. Herein, we demonstrate optimization of a biodegradable nanoparticle for efficient brain accumulation and protection of astrocytes from oxidative damage and mitochondrial dysfunctions to enhance the neuroprotection ability of astrocytes toward neurons using neurodegeneration characteristics in SOD1G93A rats. This biodegradable nanomedicine platform with the ability to accumulate in the brain has the potential to bring beneficial effects in neurodegenerative diseases by modulating the stars, astrocytes in the brain, to enhance their neuroprotective actions.

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Effect of novel quercetin pivaloyl ester on functions of adult rat microglia

Biologia ◽

10.1515/biolog-2015-0082 ◽

2015 ◽

Vol 70 (5) ◽

Cited By ~ 3

Author(s):

Marcela Kuniaková ◽

Nataša Mrvová ◽

Vladimír Knezl ◽

Lucia Račková

Keyword(s):

Neurodegenerative Diseases ◽

Replicative Senescence ◽

The Novel ◽

Beneficial Effects ◽

Adult Rat ◽

Glial Cultures ◽

Inflammatory Stimuli ◽

Oxidative Challenge ◽

The Brain

AbstractThe pathogenic mechanisms involved in the development of ageing-related neurodegenerative diseases can involve alterations of microglia, the brain counterpart of macrophages. These include microglial over-activation, replicative senescence, accumulation of autofluorescent lipofuscin and mitochondrial dysfunction. Substantial evidence suggests that dietary flavonoids are capable to modulate and probably revert the hyperactive and senescence phenotype of these cells. The present study assessed the effect of a novel semisynthetic flavonoid 3’-O-(3-chloropivaloyl)quercetin (CPQ) on the functions of adult rat microglia, isolated secondarily to the establishment of mixed glial cultures and compared it with the effect of the unmodified molecule, quercetin. CPQ suppressed NO release by lipopolysaccharide-stimulated cells more effectively than did quercetin. Unlike quercetin, CPQ inhibited the injury of cell viability due to oxidative challenge and suppressed senescence-associated β-galactosidase staining of microglia isolated from long-term mixed glial cultures. Both flavonoids tested protected the functions of microglia in response to inflammatory stimuli. Furthermore, both compounds protected the isolated microglia from adverse effects of HEPES-buffered media. This was followed by an increase of cell yields, improvement of lysosomal function, suppression of nuclear protein oxidation and inhibition of lipofuscin accumulation (at a slightly more profound effect of CPQ). In conclusion, our data support the experimental evidence suggesting beneficial effects of flavonoids in modulation of neuropathology- and ageing-related alterations of microglia. In this regard, the novel pivaloyl ester of quercetin might represent a new drug with improved potential against neurodegenerative diseases.

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Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation

Molecules ◽

10.3390/molecules27020341 ◽

2022 ◽

Vol 27 (2) ◽

pp. 341

Author(s):

Antonia Cianciulli ◽

Rosa Calvello ◽

Melania Ruggiero ◽

Maria Antonietta Panaro

Keyword(s):

Neurodegenerative Diseases ◽

Curcuma Longa ◽

Significant Risk ◽

Significant Risk Factor ◽

Low Grade ◽

Beneficial Effects ◽

Positive Effects ◽

Age Related ◽

Brain Ageing ◽

The Brain

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases.

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Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

Current Pharmaceutical Design ◽

10.2174/1381612825666190716101411 ◽

2019 ◽

Vol 25 (23) ◽

pp. 2555-2568 ◽

Cited By ~ 5

Author(s):

Rajeev Taliyan ◽

Sarathlal K. Chandran ◽

Violina Kakoty

Keyword(s):

Diabetes Mellitus ◽

Protein Trafficking ◽

Metabolic Stress ◽

Insulin Receptors ◽

Metabolic Dysfunction ◽

Beneficial Effects ◽

Glucose And Lipid Metabolism ◽

Endocrine Hormone ◽

Metabolic Conditions ◽

The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

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Excitotoxicity as a Target Against Neurodegenerative Processes

Current Pharmaceutical Design ◽

10.2174/1381612826666200113162641 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1251-1262 ◽

Cited By ~ 2

Author(s):

Octavio Binvignat ◽

Jordi Olloquequi

Keyword(s):

Neurodegenerative Diseases ◽

Effective Treatment ◽

Molecular Mechanisms ◽

Prolonged Exposure ◽

Mitochondrial Dysfunctions ◽

Beneficial Effects ◽

Clinical Investigations ◽

Turn Over ◽

Excitotoxic Cell Death ◽

Lateral Sclerosis

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.

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The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666181005093459 ◽

2019 ◽

Vol 19 (3) ◽

pp. 316-325

Author(s):

Mahdi Goudarzvand ◽

Yaser Panahi ◽

Reza Yazdani ◽

Hosein Miladi ◽

Saeed Tahmasebi ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Inflammatory Mediators ◽

Mouse Serum ◽

Enzyme Linked Immunosorbent Assay ◽

Oral Gavage ◽

Autoimmune Encephalomyelitis ◽

Beneficial Effects ◽

17Β Estradiol ◽

The Brain ◽

Experimental Autoimmune

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

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Boswellia serrata Oleo-Gum-Resin and its Effect on Memory Functions: A Review

The Natural Products Journal ◽

10.2174/2210315509666190311153819 ◽

2020 ◽

Vol 10 (4) ◽

pp. 355-363

Author(s):

Mohaddese Mahboubi ◽

Leila Mohammad Taghizadeh Kashani

Keyword(s):

Memory Loss ◽

Modern Medicine ◽

Waste Materials ◽

Boswellia Serrata ◽

Memory Functions ◽

Beneficial Effects ◽

Waste Production ◽

Nursing Mothers ◽

Traditional Practitioners ◽

The Brain

Background: In Iranian Traditional Medicine, Boswellia serrata oleo-gum resins were used for the treatment of "Nisyan". "Nisyan" was equivalent to a reduction of memory or forgetfulness. Objective: This review evaluates the traditional believes of B. serrata and memory and its effectiveness on memory loss. Methods: We extracted all traditional and modern information on B. serrata oleo-gum resin preparations and memory from scientific accessible resources (Google Scholar, PubMed, Springer, Science direct, Wiley), non-accessible resources and traditional books. Results: In traditional manuscripts, "Nisyan" is equal to memory loss in modern medicine and was believed to happen as the result of pouring the waste materials into the brain. Traditional practitioners treated "Nisyan" by inhibition of waste production in the brain or cleaning the brain from waste materials. They recommended using the plants with warming effects on the brain. It was believed that B. serrata had beneficial effects on memory functions and its memory enhancing effects have been the subject of pharmacological and clinical trial studies. Conclusion: Despite some documents on the effectiveness of B. serrata oleo-gum-resin on memory functions, there is gap between these investigations, especially in pregnant and nursing mothers. More investigations with large clinical trials are required to complete flaw in order to improve the therapeutic applications of B. serrata on memory functions.

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Is There a Brain Microbiome?

Neuroscience Insights ◽

10.1177/26331055211018709 ◽

2021 ◽

Vol 16 ◽

pp. 263310552110187

Author(s):

Christopher D Link

Keyword(s):

Animal Models ◽

Human Brain ◽

Neurodegenerative Diseases ◽

Ground Truth ◽

Healthy Human ◽

Strong Motivation ◽

The Many ◽

The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

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