scholarly journals Regional transcriptional architecture of Parkinson’s disease pathogenesis and network spread

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3072-3085 ◽  
Author(s):  
Benjamin Freeze ◽  
Sneha Pandya ◽  
Yashar Zeighami ◽  
Ashish Raj
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Disease Spread ◽  
Disease Pathogenesis ◽  
Diffusion Modelling ◽  
Network Diffusion

The role of genetics in controlling the spread of pathology between brain regions in Parkinson’s disease is largely unclear. Freeze et al. report that regional microglial abundance and transcription of immune-related and lysosomal genes predict pathology seed regions and disease spread inferred from network diffusion modelling of MRI-derived atrophy maps.

Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy

2021 ◽  
Author(s):  
Fillipe M. de Araújo ◽  
Lorena Cuenca-Bermejo ◽  
Emiliano Fernández-Villalba ◽  
Silvia L. Costa ◽  
Victor Diogenes A. Silva ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nlrp3 Inflammasome ◽  
Disease Pathogenesis

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

The key role of T cells in Parkinson's disease pathogenesis and therapy

2019 ◽  
Vol 60 ◽  
pp. 25-31 ◽  
Author(s):  
Jill K. Baird ◽  
Dennis Bourdette ◽  
Charles K. Meshul ◽  
Joseph F. Quinn
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Cells ◽  
Disease Pathogenesis

scholarly journals Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease

Glia ◽  
2015 ◽  
Vol 64 (3) ◽  
pp. 386-395 ◽  
Author(s):  
Heather L. Martin ◽  
Matteo Santoro ◽  
Sarah Mustafa ◽  
Gernot Riedel ◽  
John V. Forrester ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Immune Response ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Adaptive Immune Response ◽  
Disease Pathogenesis ◽  
Adaptive Immune

scholarly journals The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis

2017 ◽  
Vol 40 (6) ◽  
pp. 358-370 ◽  
Author(s):  
Heather D.E. Booth ◽  
Warren D. Hirst ◽  
Richard Wade-Martins
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Pathogenesis

Unveiling the Role of Cytochrome P450 (2E1) in Human Brain Specifically in Parkinson’s Disease - Literature Review

2021 ◽  
Vol 22 ◽  
Author(s):  
Amna Shah ◽  
Chin Eng Ong ◽  
Yan Pan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cytochrome P450 ◽  
Literature Review ◽  
Brain Regions ◽  
Cytochrome P450 Enzymes ◽  
Negative Effects ◽  
Drug Biotransformation ◽  
The Central Nervous System

Background: In recent years, the significance of cytochrome P450 enzymes (CYPs) has expanded beyond their role in liver. Factors such as genetics, environmental toxins, drug biotransformation and underlying diseases mediate the expression of these enzymes. Among the CYP enzymes, CYP2E1, a well-recognized monooxygenase enzyme involved in the metabolism of various endogenous and exogenous substances, plays a crucial role in the brain concerning the development of Parkinson’s disease. The expression of CYP2E1 varies in different brain regions making certain regions more vulnerable than others. CYP2E1 expression is inducible which generates tissue-damaging radicals leading to oxidative stress, mitochondrial dysfunction and ultimately neurodegeneration. Objective: Less is understood about the role of CYP2E1 in the central nervous system, therefore the purpose of the study was to investigate the relationship between the expression and activity of CYP2E1 enzyme relevant to Parkinson’s disease and to identify whether an increase in the expression of CYP2E1 is associated with neurodegeneration. Methods: The objectives of the study were achieved by implicating an unsystematic integrative literature review approach in which the literature was qualitatively analysed, critically evaluated and a new theory with an overall view of the mechanism was presented. Results : The contribution of CYP2E1 in the development of Parkinson’s disease was found to be significant as the negative effects of CYP2E1 overshadowed its protective detoxifying role. Conclusion: Overexpression of CYP2E1 seems detrimental to dopaminergic neurons, therefore, to overcome this, a synthetic biochemical is required which paves the way for further research and development of valuable biomolecules.

scholarly journals Epigenetic Study in Parkinson’s Disease: A Pilot Analysis of DNA Methylation in Candidate Genes in Brain

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 150 ◽  
Author(s):  
Luis Navarro-Sánchez ◽  
Beatriz Águeda-Gómez ◽  
Silvia Aparicio ◽  
Jordi Pérez-Tur
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Brain Regions ◽  
Epigenetic Factors ◽  
Promoter Regions ◽  
Disease Pathogenesis ◽  
Cpg Dinucleotides

Efforts have been made to understand the pathophysiology of Parkinson’s disease (PD). A significant number of studies have focused on genetics, despite the fact that the described pathogenic mutations have been observed only in around 10% of patients; this observation supports the fact that PD is a multifactorial disorder. Lately, differences in miRNA expression, histone modification, and DNA methylation levels have been described, highlighting the importance of epigenetic factors in PD etiology. Taking all this into consideration, we hypothesized that an alteration in the level of methylation in PD-related genes could be related to disease pathogenesis, possibly due to alterations in gene expression. After analysing promoter regions of five PD-related genes in three brain regions by pyrosequencing, we observed some differences in DNA methylation levels (hypo and hypermethylation) in substantia nigra in some CpG dinucleotides that, possibly through an alteration in Sp1 binding, could alter their expression.

scholarly journals Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease

2021 ◽  
Vol 22 (12) ◽  
pp. 6517
Author(s):  
Antonella Cardinale ◽  
Valeria Calabrese ◽  
Antonio de Iure ◽  
Barbara Picconi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Snare Complex ◽  
Synaptic Proteins ◽  
Prodromal Phase ◽  
Toxic Species ◽  
The Central Nervous System

Parkinson’s disease (PD) is considered the most common disorder of synucleinopathy, which is characterised by intracellular inclusions of aggregated and misfolded α-synuclein (α-syn) protein in various brain regions, and the loss of dopaminergic neurons. During the early prodromal phase of PD, synaptic alterations happen before cell death, which is linked to the synaptic accumulation of toxic α-syn specifically in the presynaptic terminals, affecting neurotransmitter release. The oligomers and protofibrils of α-syn are the most toxic species, and their overexpression impairs the distribution and activation of synaptic proteins, such as the SNARE complex, preventing neurotransmitter exocytosis and neuronal synaptic communication. In the last few years, the role of the immune system in PD has been increasingly considered. Microglial and astrocyte activation, the gene expression of proinflammatory factors, and the infiltration of immune cells from the periphery to the central nervous system (CNS) represent the main features of the inflammatory response. One of the actors of these processes is α-syn accumulation. In light of this, here, we provide a systematic review of PD-related α-syn and inflammation inter-players.

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