scholarly journals Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease

2002 ◽  
Vol 81 (6) ◽  
pp. 1285-1297 ◽  
Author(s):  
Hui-Ming Gao ◽  
Janwei Jiang ◽  
Belinda Wilson ◽  
Wanqin Zhang ◽  
Jau-Shyong Hong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Progressive Degeneration

scholarly journals Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

2015 ◽  
Vol 73 (7) ◽  
pp. 616-623 ◽  
Author(s):  
Taysa Bervian Bassani ◽  
Maria A.B.F. Vital ◽  
Laryssa K. Rauh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Inflammatory Process ◽  
Epidemiological Studies ◽  
Substantia Nigra Pars Compacta ◽  
Fine Motor ◽  
Progressive Degeneration ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

scholarly journals Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

2009 ◽  
Vol 202 (3) ◽  
pp. 431-439 ◽  
Author(s):  
Sehee Kim ◽  
Minho Moon ◽  
Seungjoon Park
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Matrix Metalloproteinase ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Substantia Nigra Pars Compacta ◽  
Matrix Metalloproteinase 3 ◽  
Glucagon Like Peptide 1 ◽  
Factor Α ◽  
Inflammatory Molecules

Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor α and interleukin-1β. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.

scholarly journals Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Hye-Sun Lim ◽  
Joong-Sun Kim ◽  
Byeong Cheol Moon ◽  
Goya Choi ◽  
Seung Mok Ryu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Neuronal Loss ◽  
B Cell Lymphoma ◽  
Nuclear Hormone Receptor ◽  
Substantia Nigra Pars Compacta ◽  
Protective Effects ◽  
Dopamine Depletion

Parkinson’s disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.

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