scholarly journals Identification of Blood-based Biomarkers for Early Stage Parkinson’s Disease

2020 ◽  
Author(s):  
Andrew Gao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Differentially Expressed ◽  
Motor Symptoms ◽  
Early Stages

AbstractParkinson’s disease (PD) affects millions of people worldwide and causes symptoms such as bradykinesia and disrupted speech. Parkinson’s disease is known to be characterized by the mass death of dopaminergic neurons in the substantia nigra region. In the status quo, PD is often diagnosed at late stages because obvious motor symptoms appear after the disease has progressed far. It is advantageous to diagnose PD before the onset of motor symptoms because treatments are often more effective at early stages. While motor symptoms usually manifest when over 50% of dopaminergic neurons in the substantia nigra are already lost, molecular signatures of PD may be present at early stages in patient blood. This study aimed to analyze several gene expression studies’ data for commonly differentially expressed genes (DEGs) in the blood of early stage PD patients. 147 DEGs were identified in at least two out of three datasets and passed cut-off criteria. A protein interaction network for the DEGs was constructed and various tools were used to identify network characteristics and hub genes. PANTHER analysis revealed that the biological process “cellular response to glucagon stimulus” was overrepresented by almost 21 times among the DEGs and “lymphocyte differentiation” by 5.98 times. Protein catabolic processes and protein kinase functions were also overrepresented. ESR1, CD19, SMAD3, FOS, CXCR5, and PRKACA may be potential biomarkers and warrant further study. Overall, the findings of the present study provide insights on molecular mechanisms of PD and provide greater confidence on which genes are differentially expressed in PD. The results also are additional evidence for the role of the immune system in PD, a topic that is gaining interest in the PD research community.

scholarly journals Autophagin-3 (ATG4C) is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding autophagin-3 (ATG4C) in the substantia nigra of patients with PD.

scholarly journals LINC00643 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Non Coding Rna ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the long intergenic non-coding RNA LINC00643 in the substantia nigra of patients with PD.

scholarly journals CDK6 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Cyclin Dependent Kinase ◽  
Gene Encoding

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray (2, 3) datasets to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the cyclin-dependent kinase CDK6 in the substantia nigra of patients with PD.

scholarly journals ID2 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray (2, 3) datasets to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the transcription factor ID2 in the substantia nigra of patients with PD.

scholarly journals C18ORF54 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Open Reading Frame ◽  
Differentially Expressed ◽  
Reading Frame ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray datasets (2, 3, 4) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of open reading frame 18 on chromosome 54 (C18ORF54) in the substantia nigra of patients with PD.

Neuroinflammation caused by activated microglia and astrocytes can contribute to the progression of pathogenic damage to substantia nigra neurons, playing a role in Parkinson's disease progression

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Molecular Pathways ◽  
Activated Microglia

Parkinson's disease progresses by a number of regionally specific cellular and molecular mechanisms. Furthermore, these pathways interact and have an influence on one another in both normal and pathological conditions. Neuroinflammation caused by activated microglia and astrocytes can contribute to the progression of pathogenic damage to substantia nigra (SN) neurons. Similarly, oxidative stress may be caused by a variety of stressors, such as contaminants in the environment or age-related mitochondrial dysfunction, leading to the production of reactive oxygen species (ROS). Dopamine auto-oxidation is a significant generator of ROS in dopaminergic neurons, resulting in neuronal oxidative stress. The high energy demands of dopaminergic neurons may result in mitochondrial dysfunction and oxidative damage as they age. Because mitophagy clears dysfunctional mitochondria from SN neurons, mutation-related abnormalities in autophagy of defective proteins might allow damaging proteins to accumulate in the cell. Because the effects of aging on these molecular pathways and cellular activities are unknown, further study into these molecular pathways and their connections in normal and sick states will be essential for developing disease-specific therapies.

scholarly journals ANK1 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding ANK1 in the substantia nigra of patients with PD.

scholarly journals KMT5B is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Histone Lysine ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3, 4) to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the histone lysine N-methyltransferase KMT5B in the substantia nigra of patients with PD.

scholarly journals KMT2A/MLL1 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3, 4) to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding KMT2A (also known as MLL1) in the substantia nigra of patients with PD.

scholarly journals Slow Motion Analysis of Repetitive Tapping (SMART) Test: Measuring Bradykinesia in Recently Diagnosed Parkinson’s Disease and Idiopathic Anosmia

2021 ◽  
pp. 1-15
Author(s):  
Cristina Simonet ◽  
Miquel A. Galmes ◽  
Christian Lambert ◽  
Richard N. Rees ◽  
Tahrina Haque ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Early Stage ◽  
Slow Motion ◽  
Motor Dysfunction ◽  
Prodromal Phase ◽  
Floor Effect ◽  
Cross Sectional ◽  
Early Stages

Background: Bradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. Methods: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. Results: People in the early stage of PD performed the task with slower velocity (p <  0.001) and with greater frequency slope than controls (p = 0.003). The combination of reduced velocity and greater frequency slope obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p = 0.001) and smaller amplitude (p <  0.001) compared with controls. Conclusion: We present a simple, proof-of-concept method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may suggest that some are in the prodromal phase of PD.

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