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

2021 ◽  
pp. 107385842199226
Author(s):  
Stellina Y. H. Lee ◽  
Nathanael J. Yates ◽  
Susannah J. Tye

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.

1996 ◽  
Vol 19 (1) ◽  
pp. 69-69
Author(s):  
A. Berardelli ◽  
R. Agostino ◽  
A. Currà ◽  
M. Manfredi

AbstractLatash & Anson's explanation of bradykinesia in patients with Parkinson's disease and cocontraction in dystonic patients is intriguing. However, the proposed adaptive changes in the central nervous system do not fit well with both clinical and experimental evidence of motor impairment in these patients. In particular, we question the explanation of: (1) the role of postural reactions and spatial accuracy in bradykinesia, (2) certain abnormalities during the execution of sequential and simultaneous movements, (3) the sudden changes in mobility (ON and OFF) of Parkinsonian patients, and (4) the meaning of reflex circuitry changes in dystonia.


2015 ◽  
Vol 7 (3) ◽  
Author(s):  
Celmir De Oliveira Vilaça ◽  
Marco Antonio Araujo Leite ◽  
Jano Alves De Souza ◽  
Marco Orsini ◽  
João Santos Pereira ◽  
...  

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic systems in the central nervous system. In migraine it is supposed to occur hyperactivation of central dopaminergic pathways. We verified the hypothesis of improved migraine in patients who manifest PD. We evaluated 109 patients with PD over 40 years (57 men and 52 women) about the presence throughout the life of migraine, as well as the possibility of improvement in migraine after the onset of motor symptoms of PD. This group was compared to a control group of 152 people (41 men and 152 women) without PD regarding the presence of migraine and its improvement. Twenty-one patients manifested migraine in the group with PD (16 women and 5 men) in which 13 reported improvement in migraine after the onset of symptoms of PD. Among the controls, 37 interviewed had migraine history (32 women and 5 men) among which 20 showed improvement. There was no significant difference when comparing the two groups (χ21:0,05=0.337; P<0.382). We were unable to relate the improvement of migraine with the emergence of PD motor signs, despite the degeneration of dopaminergic pathways of the central nervous system.


1997 ◽  
Vol 144 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Philippe Horellou ◽  
Olivier Sabaté ◽  
Marie-Hélène Buc-Caron ◽  
Jacques Mallet

Author(s):  
Vrutangkumar V. Shah ◽  
Sachin Goyal ◽  
Harish Palanthandalam-Madapusi

Parkinson’s disease is an idiopathic and degenerative disorder of the central nervous system. Among the symptoms, the tremor at rest is one of the prominent symptoms. The challenge however is that there are no definitive diagnostic test that can confirm the presence or severity of Parkinson’s disease. This is a serious handicap especially since the drugs usually prescribed to control these symptoms have serious side effects and their dosages have to be tuned extensively. Also, the exact origin of tremor is unknown. There have been recent efforts [19] to understand the mechanism behind the Parkinsonian tremor, from a control-system perspectives. From these efforts, it appears that increased sensorimotor loop delay may be a cause for Parkinsonian tremor and thus serve as a key distinguishing feature. In the current work, we adopted this hypothesis and with the help of a relatively straightforward analysis of the motor control loop along with the help of some simulation and experimental examples, we first attempt to explain several qualitative observations relating to Parkinson’s Disease. Further, we explore the possibilities of for progress tracking, diagnosis, and early diagnosis before onset of tremor using biomechanical means.


Author(s):  
Yixuan Liang ◽  
Li Cui ◽  
Jiguo Gao ◽  
Mingqin Zhu ◽  
Ying Zhang ◽  
...  

AbstractThe search for therapeutic targets for Parkinson’s disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.


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