Effects of adenosine receptor antagonists in MPTP mouse model of Parkinson’s disease: mitochondrial DNA integrity

Essawy, Soha S.; Tawfik, Mona K.; Korayem, Horya Erfan

doi:10.5114/aoms.2017.67284

Cited by 14 publications

(7 citation statements)

References 45 publications

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“…A 2A R inhibition stopped rotenone-induced motor impairment in a rat model of PD ( Fathalla et al, 2016 ). A 1 as well as A 2A R antagonists were recommended as promising candidates for treatment of PD in a recent paper ( Essawy et al, 2017 ).…”

Section: Disorders Of the Central Nervous System (Cns)mentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Disorders Of the Central Nervous System (Cns)mentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…Inhibition or absence of complex I in the respiratory chain causes neuronal apoptosis 18. For example, mitochondrial complex I is inhibited by 1-methyl-4-phenyl-pyridinium, a metabolite of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, which causes cytotoxicity in dopamine neurons 19. Mitochondrial components also show altered function under oxidative stress.…”

Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases

2019

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Oxidative phosphorylation is a source of energy production by which many cells satisfy their energy requirements. Endogenous reactive oxygen species (ROS) are by-products of oxidative phosphorylation. ROS are formed due to the inefficiency of oxidative phosphorylation, and lead to oxidative stress that affects mitochondrial metabolism. Chronic oxidative stress contributes to the onset of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The immediate consequences of oxidative stress include lipid peroxidation, protein oxidation, and mitochondrial deoxyribonucleic acid (mtDNA) mutation, which induce neuronal cell death. Mitochondrial binding of amyloid-β (Aβ) protein has been identified as a contributing factor in AD. In PD and HD, respectively, α-synuclein (α-syn) and huntingtin (Htt) gene mutations have been reported to exacerbate the effects of oxidative stress. Similarly, abnormalities in mitochondrial dynamics and the respiratory chain occur in ALS due to dysregulation of mitochondrial complexes II and IV. However, oxidative stress-induced dysfunctions in neurodegenerative diseases can be mitigated by the antioxidant function of hydrogen sulfide (H 2 S), which also acts through the potassium (K ATP /K +) ion channel and calcium (Ca 2+) ion channels to increase glutathione (GSH) levels. The pharmacological activity of H 2 S is exerted by both inorganic and organic compounds. GSH, glutathione peroxidase (Gpx), and superoxide dismutase (SOD) neutralize H 2 O 2-induced oxidative damage in mitochondria. The main purpose of this review is to discuss specific causes and effects of mitochondrial oxidative stress in neurodegenerative diseases, and how these are impacted by the antioxidant functions of H 2 S to support the development of advancements in neurodegenerative disease treatment.

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“…[43][44][45] Regarding this, recent studies has demonstrated that caffeine administration increases extracellular dopamine in the striatum in the striatum. 46,47 This indicates that caffeine supplementation may be a potential therapeutic strategy; however, given that maintenance of basal activation of adenosine A1 and A2a receptors plays an important role in antiinflammation, vasodilation, pain modulation, anti-arrhythmia, and metabolic regulation, it is important to understand that the chronic blockage via mega dose (>400 mg per day for adults) of caffeine or pharmacological antagonists against thereceptors may cause several adverse effects.…”

Section: Caffeine Supplementation and Tbimentioning

confidence: 99%

Role of Exercise and Dietary Supplementation in Attenuation of Traumatic Brain Injury in American Football

Rank¹,

Ramos²,

Addie³

et al. 2019

Sport Exerc Med Open J

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Given the prevalence of traumatic brain injuries (TBI) in contact sports such as American Football, the need for increased research in TBI has been dramatically increased over the last 20-years. TBI has two main mechanisms that cause neuronal cell death following an incident: direct axonal death and neuronal inflammation, with the latter being the most common because it persists more than a decade and chronically affects neighboring neurons. Therefore, proper management that reduces inflammation post-TBI should be stressed in order to facilitate propitious recovery. While sideline concussion protocols have been implemented in sports fields, it is important immediately to initiate recovery protocols in order to minimize the degree of progressive neuronal death caused by TBI. While difficult to individualize symptoms for each occurrence, it is essential to incorporate a pretest of cognition, memory, and balance as a means of determining the severity of TBI. Although the sports concussion assessment tool 2 has been used by collegiate and professional teams, this tool is just based on observation and comparison. Thus, more precise and advanced diagnosis using biological methods are needed to accurately assess individual symptoms, which should save lives. One example is to use serum creatine kinase (CK) levels because CK released from damaged brain tissues enters the bloodstream and thus TBI can be quickly assessed and identified. While the immediate diagnosis of TBI is one part of management, efficacious treatments of post-TBI is also critical. Regarding this, exercise and nutritional supplementation have been reported to be effective. While specific pathways of neuroprotective mechanisms remain to be elucidated, endurance exercise along with supplementation of fish oil, caffeine, and vitamin D seems to elicit neuroprotective effects. This review provides potential mechanisms responsible for exercise and nutritional supplementation-mediated neuroprotection against TBI. Since human subjects are limited to mechanistic studies requiring invasive surgical procedures, research involving animals (e.g., mouse and rat) are also introduced in this review.

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Effects of adenosine receptor antagonists in MPTP mouse model of Parkinson’s disease: mitochondrial DNA integrity

Cited by 14 publications

References 45 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases

Role of Exercise and Dietary Supplementation in Attenuation of Traumatic Brain Injury in American Football

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