Immune system and new avenues in Parkinson’s disease research and treatment

2019 ◽  
Vol 30 (7) ◽  
pp. 709-727 ◽  
Author(s):  
Ava Nasrolahi ◽  
Fatemeh Safari ◽  
Mehdi Farhoudi ◽  
Afra Khosravi ◽  
Fereshteh Farajdokht ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Loss ◽  
Disease Research ◽  
Disease Modifying Therapies ◽  
Progressive Neurodegeneration ◽  
Disease Modifying ◽  
Clinical Description ◽  
Genetic And Environmental Factors

Abstract Parkinson’s disease (PD) is a progressive neurological disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. However, although 200 years have now passed since the primary clinical description of PD by James Parkinson, the etiology and mechanisms of neuronal loss in this disease are still not fully understood. In addition to genetic and environmental factors, activation of immunologic responses seems to have a crucial role in PD pathology. Intraneuronal accumulation of α-synuclein (α-Syn), as the main pathological hallmark of PD, potentially mediates initiation of the autoimmune and inflammatory events through, possibly, auto-reactive T cells. While current therapeutic regimens are mainly used to symptomatically suppress PD signs, application of the disease-modifying therapies including immunomodulatory strategies may slow down the progressive neurodegeneration process of PD. The aim of this review is to summarize knowledge regarding previous studies on the relationships between autoimmune reactions and PD pathology as well as to discuss current opportunities for immunomodulatory therapy.

scholarly journals Studying the Pathophysiology of Parkinson’s Disease Using Zebrafish

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 197 ◽  
Author(s):  
Lisa M. Barnhill ◽  
Hiromi Murata ◽  
Jeff M. Bronstein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Disease ◽  
Dopaminergic System ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Disease Mechanisms ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Parkinson’s disease is a common neurodegenerative disorder leading to severe disability. The clinical features reflect progressive neuronal loss, especially involving the dopaminergic system. The causes of Parkinson’s disease are slowly being uncovered and include both genetic and environmental insults. Zebrafish have been a valuable tool in modeling various aspects of human disease. Here, we review studies utilizing zebrafish to investigate both genetic and toxin causes of Parkinson’s disease. They have provided important insights into disease mechanisms and will be of great value in the search for disease-modifying therapies.

scholarly journals Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease: Updated from Pathogenesis to Potential Therapeutic Target

2018 ◽  
Vol 79 (5-6) ◽  
pp. 256-265 ◽  
Author(s):  
Jinhua Chen ◽  
Ying Chen ◽  
Jiali Pu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Significant Role ◽  
Dopaminergic Neurons ◽  
Recent Progress ◽  
Therapeutic Agents ◽  
Leucine Rich Repeat ◽  
Potential Therapeutic Target ◽  
Genetic And Environmental Factors

Background: Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. Summary: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment. In this review, we discuss the role of LRRK2 in PD and recent progress in the use of LRRK2 inhibitors as therapeutic agents. Key Messages: LRRK2 plays a significant role in the pathophysiology of PD, and pharmacological inhibition of LRRK2 has become one of the most promising potential therapies for PD. Further research is warranted to determine the functions of LRRK2 and expand the applications of LRRK2 inhibitors in PD treatment.

scholarly journals Lipid-Mediated Oxidative Stress and Inflammation in the Pathogenesis of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Tahira Farooqui ◽  
Akhlaq A. Farooqui
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Platelet Activating Factor ◽  
Lipid Mediators ◽  
Unknown Etiology ◽  
Oxygen Species ◽  
Progressive Loss ◽  
Progressive Neurodegeneration

Parkinson's disease (PD) is a neurodegenerative movement disorder of unknown etiology. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, depletion of dopamine in the striatum, abnormal mitochondrial and proteasomal functions, and accumulation ofα-synuclein that may be closely associated with pathological and clinical abnormalities. Increasing evidence indicates that both oxidative stress and inflammation may play a fundamental role in the pathogenesis of PD. Oxidative stress is characterized by increase in reactive oxygen species (ROS) and depletion of glutathione. Lipid mediators for oxidative stress include 4-hydroxynonenal, isoprostanes, isofurans, isoketals, neuroprostanes, and neurofurans. Neuroinflammation is characterized by activated microglial cells that generate proinflammatory cytokines, such as TNF-αand IL-1β. Proinflammatory lipid mediators include prostaglandins and platelet activating factor, together with cytokines may play a prominent role in mediating the progressive neurodegeneration in PD.

scholarly journals Venoms as an adjunctive therapy for Parkinson’s disease: where are we now and where are we going?

2021 ◽  
Vol 7 (2) ◽  
pp. FSO642
Author(s):  
Parisa Gazerani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Treatment Strategies ◽  
Neuronal Loss ◽  
Diverse Range ◽  
Dopaminergic Neuronal Loss ◽  
New Treatment ◽  
Psychiatric Impairments

Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in the aging population. Crucially, neurodegeneration of dopaminergic neurons in PD is associated with chronic inflammation and glial activation. Besides this, bradykinesia, resting tremor, rigidity, sensory alteration, and cognitive and psychiatric impairments are also present in PD. Currently, no pharmacologically effective treatment alters the progression of the disease. Discovery and development of new treatment strategies remains a focus for ongoing investigations. For example, one approach is cell therapy to prevent dopaminergic neuronal loss or to slow PD progression. The neuroprotective role of a diverse range of natural products, including venoms from bees, scorpions, snakes and lizards, are also being tested in preclinical PD models and in humans. The main findings from recent studies that have investigated venoms as therapeutic options for PD are summarized in this special report.

scholarly journals Alterations of Plasma Galectin-3 and C3 Levels in Patients with Parkinson’s Disease

2021 ◽  
Vol 11 (11) ◽  
pp. 1515
Author(s):  
Hsiu-Chuan Wu ◽  
Kuo-Hsuan Chang ◽  
Mu-Chun Chiang ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood ◽  
Plasma Levels ◽  
Dopaminergic Neurons ◽  
Cathepsin D ◽  
The Other ◽  
Galectin 3 ◽  
Progressive Neurodegeneration ◽  
Normal Controls

Parkinson’s disease (PD) is characterized by progressive neurodegeneration of dopaminergic neurons in the ventral midbrain. The complement-phagosome pathway is involved in the pathogenesis of PD. Here we measured levels of complement-phagocytosis molecules, including galectin-3, C3, C4, and cathepsin D, in the plasma of 56 patients with PD, and 46 normal controls (NCs). Plasma levels of galectin-3 (9.93 ± 3.94 ng/mL) were significantly higher in PD patients compared with NCs (8.39 ± 1.95 ng/mL, p = 0.012), and demonstrated a positive correlation with Hoehn and Yahr stages in PD patients (R2 = 0.218, p < 0.001). On the other hand, plasma C3 levels were significantly lower in PD patients (305.27 ± 205.16 μg/mL) compared with NCs (444.34 ± 245.54 μg/mL, p = 0.002). However, the levels did not correlate with Hoehn and Yahr stages (R2 = 0.010, p = 0.469). Plasma levels of C4 and cathepsin D in PD patients were similar to those in NCs. Our results show possible altered complement-phagocytosis signals in the peripheral blood of PD patients, highlighting the potential of galectin-3 as a biomarker of PD.

scholarly journals Glial Nrf2 signaling mediates the neuroprotection exerted by Gastrodia elata Blume in Lrrk2-G2019S Parkinson's disease

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yu-En Lin ◽  
Chin-Hsien Lin ◽  
En-Peng Ho ◽  
Yi-Ci Ke ◽  
Stavroula Petridi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Loss ◽  
Missense Mutations ◽  
Gastrodia Elata ◽  
Neuroprotective Effects ◽  
G2019s Mutation ◽  
Lrrk2 G2019s

The most frequent missense mutations in familial Parkinson's disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine-Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin-induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S-induced PD remain unclear. Here, we show that these G2019S flies treated with water extracts of GE (WGE) and its bioactive compounds, gastrodin and 4-HBA, displayed locomotion improvement and dopaminergic neuron protection. WGE suppressed the accumulation and hyperactivation of G2019S proteins in dopaminergic neurons, and activated the antioxidation and detoxification factor Nrf2 mostly in the astrocyte-like and ensheathing glia. Glial activation of Nrf2 antagonizes G2019S-induced Mad/Smad signaling. Moreover, we treated LRRK2-G2019S transgenic mice with WGE and found the locomotion declines, the loss of dopaminergic neurons, and the number of hyperactive microglia were restored. WGE also suppressed the hyperactivation of G2019S proteins and regulated the Smad2/3 pathways in the mice brains. We conclude that WGE prevents locomotion defects and the neuronal loss induced by G2019S mutation via glial Nrf2/Mad signaling, unveiling a potential therapeutic avenue for PD.

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