scholarly journals Protective action of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in a mouse model of Parkinson's disease

2002 ◽  
Vol 82 (3) ◽  
pp. 615-624 ◽  
Author(s):  
T. Breidert ◽  
J. Callebert ◽  
M. T. Heneka ◽  
G. Landreth ◽  
J. M. Launay ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Protective Action ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Neuroprotective Potential of Peroxisome Proliferator Activated Receptor-αAgonist in Cognitive Impairment in Parkinson’s Disease: Behavioral, Biochemical, and PBPK Profile

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dedeepya Uppalapati ◽  
Nihar R. Das ◽  
Rahul P. Gangwal ◽  
Mangesh V. Damre ◽  
Abhay T. Sangamwar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Pbpk Modeling ◽  
Pharmacokinetic Parameters ◽  
Peroxisome Proliferator ◽  
Fenofibric Acid ◽  
Peroxisome Proliferator Activated Receptor

Parkinson’s disease (PD) is a common neurodegenerative disorder affecting 1% of the population by the age of 65 years and 4-5% of the population by the age of 85 years. PD affects functional capabilities of the patient by producing motor symptoms and nonmotor symptoms. Apart from this, it is also associated with a higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of fenofibrate, a PPAR-αagonist in cognitive impairment model in PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 µg/1 µL/side) produced significant cognitive dysfunctions. Fenofibrate treatment at 10, 30, and 100 mg/kg for twenty-five days was found to be neuroprotective and improved cognitive impairment in MPTP-induced PD model as evident from behavioral, biochemical (MDA, GSH, TNF-α, and IL-6), immunohistochemistry (TH), and DNA fragmentation (TUNEL positive cells) studies. Further, physiologically based pharmacokinetic (PBPK) modeling study was performed using GastroPlus to characterize the kinetics of fenofibric acid in the brain. A good agreement was found between pharmacokinetic parameters obtained from the actual and simulated plasma concentration-time profiles of fenofibric acid. Results of this study suggest that PPAR-αagonist (fenofibrate) is neuroprotective in PD-induced cognitive impairment.

The effect of preventive exercise on the neuroprotection in 6-hydroxydopamine-lesioned rat brain

2019 ◽  
Vol 44 (12) ◽  
pp. 1267-1275 ◽  
Author(s):  
Zeinab Rezaee ◽  
Sayed Mohammad Marandi ◽  
Hojjatallah Alaei ◽  
Fahimeh Esfarjani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Treadmill Running ◽  
Spatial Learning And Memory ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
6 Hydroxydopamine

Parkinson’s disease is characterized by neurodegeneration and learning deficiency. Physical exercise can alleviate these symptoms by increasing the expression of some effective and relevant factors. The preventive effect of 16-week treadmill running in a rat model of Parkinson’s disease, before 6-hydroxydopamine (6-OHDA) induction, was assessed. Experimental groups consisted of sedentary (SED), SED+6-OHDA, exercised (EX), and EX+6-OHDA rats. Forty-eight hours after the last session of exercise, 6-OHDA was injected into the medial forebrain bundle (MFB). One week after the injection, behavioral tests, including spatial learning and memory, were assessed through Morris water maze (MWM) and apomorphine-induced rotation. Three weeks after the injection, mRNA expression and protein levels of the transcriptional co-activator peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α), fibronectin type III domain-containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), and tyrosine hydroxylase (TH) were measured in the striatum and the hippocampus of rats by applying real-time PCR and Western blotting. The findings indicate that exposure to 6-OHDA leads to impairments in behavioral and molecular functions. Exercise training prevents and reduces the symptoms caused by dopamine toxins. The results suggest that treadmill running can exert neuroprotective and have preventive effects to reduce Parkinson’s disease symptoms. Novelty Parkinson’s disease impairs spatial learning and memory. Parkinson’s disease reduced levels of PGC-1α, FNDC5, and BDNF and increased neurodegeneration in the striatum and the hippocampus. Treadmill running before disease attenuated 6-OHDA-induced memory deficit and elevated neuroprotection. Exercise has multiple effects on memory and biochemical factors.

scholarly journals PGC-1s in the Spotlight with Parkinson’s Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3487
Author(s):  
Elena Piccinin ◽  
Anna Maria Sardanelli ◽  
Peter Seibel ◽  
Antonio Moschetta ◽  
Tiziana Cocco ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Dysfunctions ◽  
Process Failure ◽  
Cellular Pathways ◽  
Pathogenic Process

Parkinson’s disease is one of the most common neurodegenerative disorders worldwide, characterized by a progressive loss of dopaminergic neurons mainly localized in the substantia nigra pars compacta. In recent years, the detailed analyses of both genetic and idiopathic forms of the disease have led to a better understanding of the molecular and cellular pathways involved in PD, pointing to the centrality of mitochondrial dysfunctions in the pathogenic process. Failure of mitochondrial quality control is now considered a hallmark of the disease. The peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family acts as a master regulator of mitochondrial biogenesis. Therefore, keeping PGC-1 level in a proper range is fundamental to guarantee functional neurons. Here we review the major findings that tightly bond PD and PGC-1s, raising important points that might lead to future investigations.

scholarly journals Do PPAR-Gamma Agonists Have a Future in Parkinson's Disease Therapy?

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Anna R. Carta ◽  
Augusta Pisanu ◽  
Ezio Carboni
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ppar Gamma ◽  
Pathological Process ◽  
Immunomodulatory Activity ◽  
Peroxisome Proliferator ◽  
Immune Functions ◽  
Reactive Microglia ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immune Mediated

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor (PPAR)-γagonists commonly used as insulin-sensitizing drugs for the treatment of type 2 diabetes. In the last decade, PPAR-γagonists have received increasing attention for their neuroprotective properties displayed in a variety of neurodegenerative diseases, including Parkinson's disease (PD), likely related to the anti-infammatory activity of these compounds. Recent studies indicate that neuroinflammation, specifically reactive microglia, plays important roles in PD pathogenesis. Moreover, after the discovery of infiltrating activated Limphocytes in the substantia nigra (SN) of PD patients, most recent research supports a role of immune-mediated mechanisms in the pathological process leading to chronic neuroinflammation and dopaminergic degeneration. PPAR-γare highly expressed in cells of both central and peripheral immune systems, playing a pivotal role in microglial activation as well as in monocytes and T cells differentiation, in which they act as key regulators of immune responses. Here, we review preclinical evidences of PPAR-γ-induced neuroprotection in experimental PD models and highlight relative anti-inflammatory mechanisms involving either central or peripheral immunomodulatory activity. Specific targeting of immune functions contributing to neuroinflammation either directly (central) or indirectly (peripheral) may represent a novel therapeutic approach for disease modifying therapies in PD.

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