Expression of MMP-2, MMP-9, and MMP-1 and Their Endogenous Counterregulators TIMP-1 and TIMP-2 in Postmortem Brain Tissue of Parkinson's Disease

2002 ◽  
Vol 178 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Stefan Lorenzl ◽  
David S. Albers ◽  
Sabine Narr ◽  
Jason Chirichigno ◽  
M.Flint Beal
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Postmortem Brain Tissue

scholarly journals Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 368
Author(s):  
Shi-Xun Ma ◽  
Su Bin Lim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Rna Degradation ◽  
Postmortem Brain ◽  
Cell Type ◽  
New Findings ◽  
Postmortem Brain Tissue ◽  
Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

scholarly journals CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuanyuan Li ◽  
Mengyue Niu ◽  
Aonan Zhao ◽  
Wenyan Kang ◽  
Zhichun Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cxcr4 Expression ◽  
Postmortem Brain ◽  
Primary Microglia ◽  
Postmortem Brain Tissue ◽  
Culture Models ◽  
Novel Target ◽  
The Relationship ◽  
Cell Culture Models

Abstract Background The mechanisms underlying the pathogenesis and progression of Parkinson’s disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia. Methods After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation. Results We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation. Conclusions Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.

scholarly journals Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington’s Disease and Parkinson’s Disease Human Brains

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
C. Fourie ◽  
E. Kim ◽  
H. Waldvogel ◽  
J. M. Wong ◽  
A. McGregor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Immunohistochemical Analysis ◽  
Synaptic Proteins ◽  
Postmortem Brain ◽  
Postmortem Brain Tissue ◽  
Human Brains

NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs) are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in Huntington’s disease (HD) and Parkinson’s disease (PD). We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus.

scholarly journals APOE and MAPT Are Associated With Dementia in Neuropathologically Confirmed Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jon-Anders Tunold ◽  
Hanneke Geut ◽  
J. M. Annemieke Rozemuller ◽  
Sandra Pilar Henriksen ◽  
Mathias Toft ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Age At Onset ◽  
Cox Proportional Hazards ◽  
Postmortem Brain ◽  
Tissue Samples ◽  
Postmortem Brain Tissue ◽  
Ε4 Allele

Introduction: Cognitive decline and dementia are common and debilitating non-motor phenotypic features of Parkinson's disease with a variable severity and time of onset. Common genetic variation of the Apolipoprotein E (APOE) and micro-tubule associated protein tau (MAPT) loci have been linked to cognitive decline and dementia in Parkinson's disease, although studies have yielded mixed results. To further elucidate the influence of APOE and MAPT variability on dementia in Parkinson's disease, we genotyped postmortem brain tissue samples of clinically and pathologically well-characterized Parkinson's donors and performed a survival analysis of time to dementia.Methods: We included a total of 152 neuropathologically confirmed Parkinson's disease donors with or without clinical dementia during life. We genotyped known risk variants tagging the APOE ε4 allele and MAPT H1/H2 inversion haplotype. Cox proportional hazards regression analyses adjusted for age at onset, sex and genetic principal components were performed to assess the association between the genetic variants and time from motor onset to onset of dementia.Results: We found that both the APOE ε4 allele (HR 1.82, 95 % CI 1.16–2.83, p = 0.009) and MAPT H1-haplotype (HR 1.71, 95 % CI 1.06–2.78, p = 0.03) were associated with earlier development of dementia in patients with Parkinson's disease.Conclusion: Our results provide further support for the importance of APOE ε4 and MAPT H1-haplotype in the etiology of Parkinson's disease dementia, with potential future relevance for risk stratification and patient selection for clinical trials of therapies targeting cognitive decline in Parkinson's disease.

scholarly journals Sepiapterin reductase expression is increased in Parkinson's disease brain tissue

2007 ◽  
Vol 1139 ◽  
pp. 42-47 ◽  
Author(s):  
Jennifer E. Tobin ◽  
Jing Cui ◽  
Jemma B. Wilk ◽  
Jeanne C. Latourelle ◽  
Jason M. Laramie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Tissue ◽  
Sepiapterin Reductase

scholarly journals Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Preeti Singh ◽  
Peter S. Hanson ◽  
Christopher M. Morris
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Neural Cells ◽  
Compensatory Mechanism ◽  
Postmortem Brain Tissue ◽  
Lysine Deacetylases ◽  
Neuronal Stress

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along withα-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation ofα-synuclein aggregates but showed minimal colocalisation withα-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

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