Morphometric Parameters of the Neurodegenerative Process in Parkinson’s Disease and Chronic Cerebral Ischemia

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

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Inflammatory Mechanisms in Parkinson’s Disease: From Pathogenesis to Targeted Therapies

The Neuroscientist ◽

10.1177/1073858421992265 ◽

2021 ◽

pp. 107385842199226

Author(s):

Stellina Y. H. Lee ◽

Nathanael J. Yates ◽

Susannah J. Tye

Keyword(s):

Parkinson’S Disease ◽

Central Nervous System ◽

Parkinson's Disease ◽

Nervous System ◽

Immune Cells ◽

Critical Factor ◽

Neurodegenerative Process ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Novel Target

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.

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Cell-Death Mechanisms in Neurodegenerative Diseases: Diversity Among Cerebral Ischemia, Parkinson's Disease, and Huntington's Disease

Essentials of Apoptosis ◽

10.1385/1-59259-361-5:211 ◽

2003 ◽

pp. 211-224

Author(s):

R. Anne Stetler ◽

Jun Chen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Cerebral Ischemia ◽

Neurodegenerative Diseases ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Cell Death Mechanisms

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Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

Biomolecules ◽

10.3390/biom10050703 ◽

2020 ◽

Vol 10 (5) ◽

pp. 703 ◽

Cited By ~ 1

Author(s):

Mercè Pallàs ◽

Santiago Vázquez ◽

Coral Sanfeliu ◽

Carles Galdeano ◽

Christian Griñán-Ferré

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Epoxide Hydrolase ◽

Active Role ◽

Soluble Epoxide Hydrolase ◽

Hydrolytic Activity ◽

Neurodegenerative Process ◽

Anti Inflammatory

Neuroinflammation is a crucial process associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Several pieces of evidence suggest an active role of lipid mediators, especially epoxy-fatty acids (EpFAs), in the genesis and control of neuroinflammation; 14,15-epoxyeicosatrienoic acid (14,15-EET) is one of the most commonly studied EpFAs, with anti-inflammatory properties. Soluble epoxide hydrolase (sEH) is implicated in the hydrolysis of 14,15-EET to its corresponding diol, which lacks anti-inflammatory properties. Preventing EET degradation thus increases its concentration in the brain through sEH inhibition, which represents a novel pharmacological approach to foster the reduction of neuroinflammation and by end neurodegeneration. Recently, it has been shown that sEH levels increase in brains of PD patients. Moreover, the pharmacological inhibition of the hydrolase domain of the enzyme or the use of sEH knockout mice reduced the deleterious effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. This paper overviews the knowledge of sEH and EETs in PD and the importance of blocking its hydrolytic activity, degrading EETs in PD physiopathology. We focus on imperative neuroinflammation participation in the neurodegenerative process in PD and the putative therapeutic role for sEH inhibitors. In this review, we also describe highlights in the general knowledge of the role of sEH in the central nervous system (CNS) and its participation in neurodegeneration. We conclude that sEH is one of the most promising therapeutic strategies for PD and other neurodegenerative diseases with chronic inflammation process, providing new insights into the crucial role of sEH in PD pathophysiology as well as a singular opportunity for drug development.

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Positive association of Parkinson’s disease with ankylosing spondylitis: a nationwide population-based study

Journal of Translational Medicine ◽

10.1186/s12967-020-02629-w ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Fu-Chiang Yeh ◽

Hsiang-Cheng Chen ◽

Yu-Ching Chou ◽

Cheng-Li Lin ◽

Chia-Hung Kao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ankylosing Spondylitis ◽

Cox Model ◽

Positive Association ◽

Underlying Mechanism ◽

Population Based ◽

Neurodegenerative Process ◽

Increased Risk ◽

Using Data

Abstract Background Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson’s disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. Methods A population-based matched cohort study was performed using data from the 2000–2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. Results This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p < .001). Particularly, AS cohort to non-AS cohort relative risk of PD significantly increased for the patients aged below 49 and above 65 years (aHR 4.70, p < .001; aHR 1.69, p < .001, respectively) and the patients with and without comorbidities (aHR 1.61, p < .001; aHR 2.71, p < .001, respectively). Furthermore, NSAID use was associated with lower risk of PD (aHR 0.69, p < .05). However, the risk of PD was higher (aHR 2.40, p < .01) in patients with AS receiving immunosuppressants than in those not receiving (aHR 1.70, p < .001). Conclusions Patients with AS had an increased risk of PD which might be related to underlying chronic inflammation. Further research is required to elucidate the underlying mechanism.

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Progress in the pathogenesis and genetics of Parkinson's disease

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2008.2273 ◽

2008 ◽

Vol 363 (1500) ◽

pp. 2215-2227 ◽

Cited By ~ 52

Author(s):

Yoshikuni Mizuno ◽

Nobutaka Hattori ◽

Shin-ichiro Kubo ◽

Shigeto Sato ◽

Kenya Nishioka ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Mechanisms ◽

Disease Process ◽

Ubiquitin Proteasome System ◽

Neurodegenerative Process ◽

Molecular Events ◽

Ubiquitin Proteasome ◽

Sporadic Parkinson’S Disease ◽

Synuclein Proteins

Recent progresses in the pathogenesis of sporadic Parkinson's disease (PD) and genetics of familial PD are reviewed. There are common molecular events between sporadic and familial PD, particularly between sporadic PD and PARK1 -linked PD due to α - synuclein ( SNCA ) mutations. In sporadic form, interaction of genetic predisposition and environmental factors is probably a primary event inducing mitochondrial dysfunction and oxidative damage resulting in oligomer and aggregate formations of α-synuclein. In PARK1 -linked PD, mutant α-synuclein proteins initiate the disease process as they have increased tendency for self-aggregation. As highly phosphorylated aggregated proteins are deposited in nigral neurons in PD, dysfunctions of proteolytic systems, i.e. the ubiquitin–proteasome system and autophagy–lysosomal pathway, seem to be contributing to the final neurodegenerative process. Studies on the molecular mechanisms of nigral neuronal death in familial forms of PD will contribute further on the understanding of the pathogenesis of sporadic PD.

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