Therapeutic Potential of Dietary Polyphenols against Brain Ageing and Neurodegenerative Disorders

2010 ◽  
pp. 27-35 ◽  
Author(s):  
Giovanni Scapagnini ◽  
Calogero Caruso ◽  
Vittorio Calabrese
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
Dietary Polyphenols ◽  
Brain Ageing

Therapeutic Potential of Cannabinoids in Neurodegenerative Disorders: A Selective Review

2014 ◽  
Vol 20 (13) ◽  
pp. 2218-2230 ◽  
Author(s):  
Latha Velayudhan ◽  
Erik Diepen ◽  
Mangesh Marudkar ◽  
Oliver Hands ◽  
Srinivas Suribhatla ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
Selective Review

scholarly journals Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation

2020 ◽  
Vol 6 (46) ◽  
pp. eabc1428
Author(s):  
A. Nakano-Kobayashi ◽  
A. Fukumoto ◽  
A. Morizane ◽  
D. T. Nguyen ◽  
T. M. Le ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Neuronal Survival ◽  
Disease Model ◽  
Neuronal Loss ◽  
Induced Pluripotent Stem Cell ◽  
Related Factor ◽  
Induced Pluripotent ◽  
Novel Therapeutic

Neurodegenerative disorders are caused by progressive neuronal loss, and there is no complete treatment available yet. Neuroinflammation is a common feature across neurodegenerative disorders and implicated in the progression of neurodegeneration. Dysregulated activation of microglia causes neuroinflammation and has been highlighted as a treatment target in therapeutic strategies. Here, we identified novel therapeutic candidate ALGERNON2 (altered generation of neurons 2) and demonstrate that ALGERNON2 suppressed the production of proinflammatory cytokines and rescued neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced Parkinson’s disease model. ALGERNON2 stabilized cyclinD1/p21 complex, leading to up-regulation of nuclear factor erythroid 2–related factor 2 (Nrf2), which contributes to antioxidative and anti-inflammatory responses. Notably, ALGERNON2 enhanced neuronal survival in other neuroinflammatory conditions such as the transplantation of induced pluripotent stem cell–derived dopaminergic neurons into murine brains. In conclusion, we present that the microglial potentiation of the p21-Nrf2 pathway can contribute to neuronal survival and provide novel therapeutic potential for neuroinflammation-triggered neurodegeneration.

Hepcidin and its therapeutic potential in neurodegenerative disorders

2020 ◽  
Vol 40 (2) ◽  
pp. 633-653 ◽  
Author(s):  
Zhong‐Ming Qian ◽  
Ya Ke
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Potential

scholarly journals Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3064
Author(s):  
Youngpyo Nam ◽  
Gyeong Joon Moon ◽  
Sang Ryong Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Active Form ◽  
Mammalian Target Of Rapamycin ◽  
Regulatory System ◽  
Neuronal Population ◽  
Vital Role

Neurotrophic factors (NTFs) are essential for cell growth, survival, synaptic plasticity, and maintenance of specific neuronal population in the central nervous system. Multiple studies have demonstrated that alterations in the levels and activities of NTFs are related to the pathology and symptoms of neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. Hence, the key molecule that can regulate the expression of NTFs is an important target for gene therapy coupling adeno-associated virus vector (AAV) gene. We have previously reported that the Ras homolog protein enriched in brain (Rheb)–mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. AAV transduction using a constitutively active form of Rheb exerts a neuroprotective effect through the upregulation of NTFs, thereby promoting the neurotrophic interaction between astrocytes and neurons in AD conditions. These findings suggest the role of Rheb as an important regulator of the regulatory system of NTFs to treat neurodegenerative diseases. In this review, we present an overview of the role of Rheb in neurodegenerative diseases and summarize the therapeutic potential of AAV serotype 1 (AAV1)-Rheb(S16H) transduction in the treatment of neurodegenerative disorders, focusing on diseases, such as AD and PD.

scholarly journals Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites

2016 ◽  
Vol 113 (19) ◽  
pp. 5435-5440 ◽  
Author(s):  
Carlo Breda ◽  
Korrapati V. Sathyasaikumar ◽  
Shama Sograte Idrissi ◽  
Francesca M. Notarangelo ◽  
Jasper G. Estranero ◽  
...  
Keyword(s):  
Quinolinic Acid ◽  
Neurodegenerative Disorders ◽  
Kynurenic Acid ◽  
Therapeutic Potential ◽  
Fruit Fly ◽  
Kynurenine Pathway ◽  
Locomotor Performance ◽  
Potential Treatment ◽  
Regulatory Enzymes ◽  
Therapeutic Benefits

Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeutic potential of inhibiting two critical regulatory enzymes in this pathway—kynurenine-3-monooxygenase (KMO) and tryptophan-2,3-dioxygenase (TDO). Much evidence indicates that the efficacy of KMO inhibition arises from normalizing an imbalance between neurotoxic [3-hydroxykynurenine (3-HK); quinolinic acid (QUIN)] and neuroprotective [kynurenic acid (KYNA)] KP metabolites. However, it is not clear if TDO inhibition is protective via a similar mechanism or if this is instead due to increased levels of TRP—the substrate of TDO. Here, we find that increased levels of KYNA relative to 3-HK are likely central to the protection conferred by TDO inhibition in a fruit fly model of Huntington’s disease and that TRP treatment strongly reduces neurodegeneration by shifting KP flux toward KYNA synthesis. In fly models of Alzheimer’s and Parkinson’s disease, we provide genetic evidence that inhibition of TDO or KMO improves locomotor performance and ameliorates shortened life span, as well as reducing neurodegeneration in Alzheimer's model flies. Critically, we find that treatment with a chemical TDO inhibitor is robustly protective in these models. Consequently, our work strongly supports targeting of the KP as a potential treatment strategy for several major neurodegenerative disorders and suggests that alterations in the levels of neuroactive KP metabolites could underlie several therapeutic benefits.

scholarly journals Revisiting nicotine’s role in the ageing brain and cognitive impairment

2017 ◽  
Vol 28 (7) ◽  
pp. 767-781 ◽  
Author(s):  
Alireza Majdi ◽  
Farzin Kamari ◽  
Manouchehr Seyedi Vafaee ◽  
Saeed Sadigh-Eteghad
Keyword(s):  
Cognitive Impairment ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Therapeutic Potential ◽  
Amyloid Β ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Pharmacological Chaperone ◽  
Age Related ◽  
Brain Ageing

AbstractBrain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment.

scholarly journals Viewpoint: Mechanisms of Action and Therapeutic Potential of Neurohormetic Phytochemicals

Dose-Response ◽  
2007 ◽  
Vol 5 (3) ◽  
pp. dose-response.0 ◽  
Author(s):  
Mark. P. Mattson ◽  
Tae Gen Son ◽  
Simonetta Camandola
Keyword(s):  
Animal Models ◽  
Neurodegenerative Disorders ◽  
Histone Deacetylases ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Disease Process ◽  
Antioxidant Response ◽  
Mechanisms Of Action ◽  
Cellular Stress Response ◽  
Vegetables And Fruits

The nervous system is of fundamental importance in the adaptive (hormesis) responses of organisms to all types of stress, including environmental “toxins”. Phytochemicals present in vegetables and fruits are believed to reduce the risk of several major diseases including cardiovascular disease, cancers and neurodegenerative disorders. Although antioxidant properties have been suggested as the basis of health benefits of phytochemicals, emerging findings suggest a quite different mechanism of action. Many phytochemicals normally function as toxins that protect the plants against insects and other damaging organisms. However, at the relatively low doses consumed by humans and other mammals these same “toxic” phytochemicals activate adaptive cellular stress response pathways that can protect the cells against a variety of adverse conditions. Recent findings have elucidated hormetic mechanisms of action of phytochemicals (e.g., resveratrol, curcumin, sulforaphanes and catechins) using cell culture and animal models of neurological disorders. Examples of hormesis pathways activated by phytochemicals include the transcription factor Nrf-2 which activates genes controlled by the antioxidant response element, and histone deacetylases of the sirtuin family and FOXO transcription factors. Such hormetic pathways stimulate the production of antioxidant enzymes, protein chaperones and neurotrophic factors. In several cases neurohormetic phytochemicals have been shown to suppress the disease process in animal models relevant to neurodegenerative disorders such as Alzheimer's and Parkinson's diseaess, and can also improve outcome following a stroke. We are currently screening a panel of biopesticides in order to establish hormetic doses, neuroprotective efficacy, mechanisms of action and therapeutic potential as dietary supplements.

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