scholarly journals Inflammatory Mechanisms of Neurodegeneration in Toxin-Based Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Darcy Litteljohn ◽  
Emily Mangano ◽  
Melanie Clarke ◽  
Jessica Bobyn ◽  
Kerry Moloney ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Proinflammatory Cytokines ◽  
Inflammatory Factors ◽  
Toxin Exposure ◽  
Environmental Agents ◽  
Inflammatory Processes ◽  
Midbrain Dopamine ◽  
Necrosis Factor

Parkinson's disease (PD) has been associated with exposure to a variety of environmental agents, including pesticides, heavy metals, and organic pollutants; and inflammatory processes appear to constitute a common mechanistic link among these insults. Indeed, toxin exposure has been repeatedly demonstrated to induce the release of oxidative and inflammatory factors from immunocompetent microglia, leading to damage and death of midbrain dopamine (DA) neurons. In particular, proinflammatory cytokines such as tumor necrosis factor-αand interferon-γ, which are produced locally within the brain by microglia, have been implicated in the loss of DA neurons in toxin-based models of PD; and mounting evidence suggests a contributory role of the inflammatory enzyme, cyclooxygenase-2. Likewise, immune-activating bacterial and viral agents were reported to have neurodegenerative effects themselves and to augment the deleterious impact of chemical toxins upon DA neurons. The present paper will focus upon the evidence linking microglia and their inflammatory processes to the death of DA neurons following toxin exposure. Particular attention will be devoted to the possibility that environmental toxins can activate microglia, resulting in these cells adopting a “sensitized” state that favors the production of proinflammatory cytokines and damaging oxidative radicals.

scholarly journals Evidence of Inflammatory System Involvement in Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yinxia Chao ◽  
Siew Cheng Wong ◽  
Eng King Tan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune Cells ◽  
Inflammatory Factors ◽  
Environmental Agents ◽  
Differential Exposure ◽  
Peripheral Immune Cells ◽  
Inflammatory System

Parkinson’s disease (PD) is a chronic neurodegenerative disease underpinned by both genetic and environmental etiologic factors. Recent findings suggest that inflammation may be a pathogenic factor in the onset and progression of both familial and sporadic PD. Understanding the precise role of inflammatory factors in PD will likely lead to understanding of how the disease arises.In vivoevidence for inflammation in PD includes dysregulated molecular mediators such as cytokines, complement system and its receptors, resident microglial activation, peripheral immune cells invasion, and altered composition and phenotype of peripheral immune cells. The growing awareness of these factors has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Influences of ageing and differential exposure to environmental agents suggest potential host-pathogen specific pathophysiologic factors. There is a clear need for research to further unravel the pathophysiologic role of immunity in PD, with the potential of developing new therapeutic targets for this debilitating condition.

scholarly journals Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Wei Huang ◽  
Qiankun Lv ◽  
Yunfei Xiao ◽  
Zhen Zhong ◽  
Binbin Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Human Genetics ◽  
Neurodegenerative Disorder ◽  
Inflammatory Factors ◽  
Inflammatory Mechanism

Parkinson’s disease is a neurodegenerative disorder with an inflammatory response as the core pathogenic mechanism. Previous human genetics findings support the view that the loss of TREM2 function will aggravate neurodegeneration, and TREM2 is one of the most highly expressed receptors in microglia. However, the role of TREM2 in the inflammatory mechanism of PD is not clear. In our study, it was found both in vivo and in vitro that the activation of microglia not only promoted the secretion of inflammatory factors but also decreased the level of TREM2 and inhibited the occurrence of autophagy. In contrast, an increase in the level of TREM2 decreased the expression of inflammatory factors and enhanced the level of autophagy through the p38 MAPK/mTOR pathway. Moreover, increased TREM2 expression significantly decreased the apoptosis of dopaminergic (DA) neurons and improved the motor ability of PD mice. In summary, TREM2 is an important link between the pathogenesis of PD and inflammation. Our study provides a new view for the mechanism of TREM2 in PD and reveals TREM2 as a potential therapeutic target for PD.

scholarly journals Kinin Peptides Enhance Inflammatory and Oxidative Responses Promoting Apoptosis in a Parkinson’s Disease Cellular Model

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Anna Niewiarowska-Sendo ◽  
Andrzej Kozik ◽  
Ibeth Guevara-Lora
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Receptor Expression ◽  
Cellular Model ◽  
Enhanced Production ◽  
Kinin Receptors ◽  
Kinin Receptor ◽  
Inflammatory Processes

Kinin peptides ubiquitously occur in nervous tissue and participate in inflammatory processes associated with distinct neurological disorders. These substances have also been demonstrated to promote the oxidative stress. On the other hand, the importance of oxidative stress and inflammation has been emphasized in disorders that involve the neurodegenerative processes such as Parkinson’s disease (PD). A growing number of reports have demonstrated the increased expression of kinin receptors in neurodegenerative diseases. In this study, the effect of bradykinin and des-Arg10-kallidin, two representative kinin peptides, was analyzed with respect to inflammatory response and induction of oxidative stress in a PD cellular model, obtained after stimulation of differentiated SK-N-SH cells with a neurotoxin, 1-methyl-4-phenylpyridinium. Kinin peptides caused an increased cytokine release and enhanced production of reactive oxygen species and NO by cells. These changes were accompanied by a loss of cell viability and a greater activation of caspases involved in apoptosis progression. Moreover, the neurotoxin and kinin peptides altered the dopamine receptor 2 expression. Kinin receptor expression was also changed by the neurotoxin. These results suggest a mediatory role of kinin peptides in the development of neurodegeneration and may offer new possibilities for its regulation by using specific antagonists of kinin receptors.

scholarly journals A Case-Control Association Study of RANTES (-28C>G) Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Nilufer Sahin-Calapoglu ◽  
Serpil Demirci ◽  
Mustafa Calapoglu ◽  
Baris Yasar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Chemokine Receptors ◽  
Case Control ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Inflammatory Processes ◽  
Control Association

Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinson’s disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86–347.24 and 1.74–591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01–0.63], p=0.019). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk.

scholarly journals The role of trophic factors and inflammatory processes in physical activity-induced neuroprotection in Parkinson’s disease

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Ewelina Pałasz ◽  
Agnieszka Bąk ◽  
Anna Gąsiorowska ◽  
Grażyna Niewiadomska
Keyword(s):  
Physical Activity ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Supportive Therapy ◽  
Trophic Factors ◽  
Moderate Physical Activity ◽  
Motor Impairments ◽  
Current State ◽  
Inflammatory Processes

Glial cells and neurotrophins play an important role in maintaining homeostasis of the CNS. Disturbances of their function can lead to a number of nervous system diseases, including Parkinson’s disease (PD). Current clinical studies provide evidence that moderate physical activity adapted to the health status of PD patients can support pharmacological treatment, slow down the onset of motor impairments, and extend the patients period of independence. Physical activity, by stimulating the production and release of endogenous trophic factors, prevents the neurodegeneration of dopaminergic neurons via inhibition of inflammatory processes and the reduction of oxidative stress. The aim of this study is to present the current state of knowledge for the anti-inflammatory and neuroprotective properties of physical activity as a supportive therapy in Parkinson’s disease.

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