scholarly journals Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

2017 ◽  
Vol 114 (10) ◽  
pp. 2735-2740 ◽  
Author(s):  
Holly Green ◽  
Xiaoqun Zhang ◽  
Katarina Tiklova ◽  
Nikolaos Volakakis ◽  
Lovisa Brodin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Nk Cell ◽  
The Body ◽  
Postmortem Brain ◽  
Cytotoxic T Cell ◽  
Mrna Levels ◽  
Comorbid Depression ◽  
Protein Levels

Individuals with Parkinson’s disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

scholarly journals Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson’s disease

2021 ◽  
Author(s):  
Fiona Dick ◽  
Ole-Bjørn Tysnes ◽  
Guido Werner Alves ◽  
Gonzalo S. Nido ◽  
Charalampos Tzoulis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Level ◽  
Spatial Separation ◽  
Healthy Ageing ◽  
Mrna Levels ◽  
Protein Levels ◽  
A Genome ◽  
Genes Encoding ◽  
Ageing Brain

AbstractThe correlation between mRNA and protein levels has been shown to decline in the ageing brain, possibly reflecting age-dependent changes in the proteostasis. It is thought that impaired proteostasis may be implicated in the pathogenesis of Parkinson’s disease (PD), but evidence derived from the patient brain is currently limited. Here, we hypothesized that if impaired proteostasis occurs in PD, this should be reflected in the form of altered correlation between transcriptome and proteome compared to healthy ageing.To test this hypothesis, we integrated transcriptomic data with proteomics from prefrontal cortex tissue of 17 PD patients and 11 demographically matched healthy controls and assessed gene-specific correlations between RNA and protein level. To control for the effects of ageing, brain samples from 4 infants were included in the analyses.In the healthy aged brain, we observed a genome-wide decreased correlation between mRNA and protein levels. Moreover, a group of genes encoding synaptic vesicle proteins exhibited inverse correlations. This phenomenon likely reflects the spatial separation of mRNA and protein into the neuronal soma and synapsis, respectively, commonly characterizing these genes. Most genes showed a significantly lower correlation between mRNA and protein levels in PD compared to neurologically healthy ageing, consistent with a proteome-wide decline in proteostasis. Genes showing an inverse correlation in PD were enriched for proteasome subunits, suggesting that these proteins show accentuated spatial separation of transcript and protein between the soma and axon/synapses in PD neurons. Moreover, the PD brain was characterized by increased positive mRNA-protein correlation for some genes encoding components of the mitochondrial respiratory chain, suggesting these may require tighter regulation in the face of mitochondrial pathology characterizing the PD brain.Our results are highly consistent with a proteome-wide impairment of proteostasis in the PD brain and strongly support the hypothesis that aberrant proteasomal function is implicated in the pathogenesis of PD. Moreover, our findings have important implications for the correct interpretation of differential gene expression studies in PD. In the presence of disease-specific altered coupling of transcriptome and proteome, measured differences in mRNA levels cannot be used to infer changes at the protein-level and should be supplemented with direct determination of proteins nominated by the analyses.

scholarly journals Da-Bu-Yin-Wan and Qian-Zheng-San to Neuroprotect the Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Gang Gong ◽  
Hong-Mei Sun ◽  
Yi Zhang ◽  
Shu-Jing Zhang ◽  
Yu-Shan Gao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neuroprotective Effect ◽  
Firefly Luciferase ◽  
Dopamine Neurons ◽  
Behavioral Impairment ◽  
Neuroprotective Effects ◽  
Atp Level ◽  
Protein Levels

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson’s disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATPchannel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATPchannel subunit expressions.

Which Drug for Parkinsonism? Walking, Stiffness, Tremor, and Slowness

2013 ◽  
Author(s):  
J. Eric Ahlskog
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
The Body ◽  
Brain Dopamine ◽  
Arm Swing ◽  
Repetitive Movements ◽  
The Brain ◽  
Repetitive Motor

In Chapters 1 and 4, we briefly summarized the symptoms of parkinsonism. Parkinsonism implies movement problems that are typical of Parkinson’s disease. They remain treatment issues during the lifetime of people with Parkinson’s disease, even if dementia develops. Similarly, parkinsonism also typically occurs in DLB, although to variable degrees. In these disorders parkinsonism primarily reflects low brain dopamine levels and improves with dopamine replacement therapy, often markedly. Parkinsonism occurs when a region of the brain called the basal ganglia ceases to work properly (see Figure 4.2 in Chapter 4). As discussed in Chapter 4, the substantia nigra is a crucial regulator of basal ganglia activity, which is mediated by dopamine release in the striatum. The substantia nigra degenerates in these Lewy disorders and, as a result, brain dopamine declines. With a decline in dopamine, movement slows. Bradykinesia is the medical term for such slowness. This manifests as not only slowed movement but also less movement and smaller than normal movements. Unconscious automatic movements, such as blinking or arm swing, diminish. A unique tremor of the hands (sometimes legs) often develops when these limbs are in a relaxed position (rest tremor). For unknown reasons, the brain is not affected symmetrically, hence, neither is the body. Typically, one side of the body is much more impaired than the other. The extent to which these symptoms develop differs from person to person and includes various combinations of the following components. The slowness may be apparent on one or both sides of the body. For example, one leg may lag behind when walking. The overall appearance is characterized by moving much slower than expected for one’s age. The person feels as if they are moving in molasses—everything slows down. Many of our daily activities involve repeated small movements, such as writing or brushing teeth. In the Lewy conditions of DLB and PDD, the size (amplitude) of repetitive movements diminishes, impairing the activity. This is exemplified by the small handwriting of someone with parkinsonism, termed micrographia. Clinicians assess repetitive motor function by asking the patient to repetitively tap the thumb and index finger.

Weight Distribution Monitoring System for Patients With Parkinson’s Disease

2018 ◽  
Author(s):  
Matthew Dickens ◽  
Ameya Wadekar ◽  
Karan Subhash Bhutada ◽  
Pham Huy Nguyen ◽  
Shannon Jameson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Transmission Line ◽  
Monitoring System ◽  
Weight Distribution ◽  
Corpus Striatum ◽  
The Body ◽  
Brain Disorder ◽  
Intentional Movement

Parkinson’s disease is a neurodegenerative brain disorder that occurs when a patient’s body stops producing dopamine. This chemical is essential in transferring motor commands between the substantia nigra and the corpus striatum which enables smooth, intentional movement in the body. Because this transmission line is degrading, about 68% of the Parkinson’s population reports falling [1].

Hyperechogenicity of substantia nigra in Parkinson's disease – Searching for genetic predictors

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
C Funke ◽  
A Soehn ◽  
C Schulte ◽  
M Bonin ◽  
C Klein ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Genetic Predictors

SPECT-Befunde bei Hemiparkinson-Syndrom mit 99mTc-HMPAO

1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Neuronal Activity ◽  
Tracer Uptake ◽  
The Body ◽  
99Mtc Hmpao ◽  
Do So

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.

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