Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson’s disease mice model
- 9 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular and Cellular Biochemistry
- Vol. 465 (1-2), 89-102
- https://doi.org/10.1007/s11010-019-03670-0
Abstract
Parkinson’s disease (PD) is the second common age-related neurodegenerative disease. It is characterized by control loss of voluntary movements control, resting tremor, postural instability, bradykinesia, and rigidity. The aim of the present work is to evaluate curcumin, niacin, dopaminergic and non-dopaminergic drugs in mice model of Parkinson’s disease through behavioral, biochemical, genetic and histopathological observations. Mice treated with rotenone rerecorded significant increase in adenosine A2A receptor (A2AR) gene expression, α synuclein, acetylcholinesterase (AchE), malondialdehyde (MDA), angiotensin-II (Ang-II), c-reactive protein (CRP), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels as compared with the control group. While, significant decrease in dopamine (DA), norepinephrine (NE), serotonin (5-HT), superoxide dismutase (SOD), reduced glutathione (GSH), ATP, succinate and lactate dehydrogenases (SDH &LDH) levels were detected. Treatment with curcumin, niacin, adenosine A2AR antagonist; ZM241385 and their combination enhanced the animals’ behavior and restored all the selected parameters with variable degrees of improvement. The brain histopathological features of hippocampal and substantia nigra regions confirmed our results. In conclusion, the combination of curcumin, niacin and ZM241385 recorded the most potent treatment effect in Parkinsonism mice followed by ZM241385, as a single treatment. ZM241385 succeeded to antagonize adenosine A2A receptor by diminishing its gene expression and ameliorating all biochemical parameters under investigation. The newly investigated agent; ZM241385 has almost the same pattern of improvement as the classical drug; Sinemet®. This could shed the light to the need of detailed studies on ZM241385 for its possible role as a promising treatment against PD. Additionally, food supplements such as curcumin and niacin were effective in Parkinson’s disease eradication.Keywords
This publication has 78 references indexed in Scilit:
- Renoprotective effect of the antioxidant curcumin: Recent findingsRedox Biology, 2013
- Caudo‐rostral brain spreading of α‐synuclein through vagal connectionsEMBO Molecular Medicine, 2013
- Niaspan increases axonal remodeling after stroke in type 1 diabetes ratsNeurobiology of Disease, 2012
- Expression of angiotensinogen and receptors for angiotensin and prorenin in the monkey and human substantia nigra: an intracellular renin–angiotensin system in the nigraBrain Structure and Function, 2012
- Niaspan enhances vascular remodeling after stroke in type 1 diabetic ratsExperimental Neurology, 2011
- Adenosine A2A receptor gene disruption protects in an α‐synuclein model of Parkinson's diseaseAnnals of Neurology, 2011
- High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratioProceedings of the National Academy of Sciences of the United States of America, 2010
- Specific Inhibition of NEIL-initiated Repair of Oxidized Base Damage in Human Genome by Copper and IronOnline Journal of Public Health Informatics, 2010
- Behavioral phenotyping of mouse models of Parkinson's diseaseBehavioural Brain Research, 2010
- Angiotensin II revisited: new roles in inflammation, immunology and agingEMBO Molecular Medicine, 2010