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Research Article
Ashmita Dey
Jadavpur University
Corresponding Author
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Parkinson's Disease is a common neurodegenerative disease. The differential expression of alpha-synuclein within Lewy Bodies leads to this disease. Some missense mutations of alpha-synuclein may resultant in functional aberrations. In this study, our objective is to verify the functional adaptation due to early and late-onset mutation which can trigger or control the rate of alpha-synuclein aggregation. In this regard, we have proposed a computational model to study the difference and/or similarities among the Wild type alpha-synuclein and two mutations G51D and E46K which are responsible for slow and fast aggregation respectively. Evolutionary sequence space analysis is also performed in this experiment. Subsequently, a comparative study has been performed between structural information and sequence space outcomes. The study shows the structural variability among the selected subtypes. This information assists inter pathway modeling due to mutational aberrations. Based on the structural variability, we have identified the protein-protein interaction partners for each protein that helps to increase the robustness of the inter-pathway connectivity. As per the inter-pathway networks, drug addiction has clear impacts on both the mutations i.e., G51D-slow, and E46K-fast and can be considered as the reason for early-onset Parkinson’s Disease. Finally, three top pathways associated with drug addiction viz., Amphetamine addiction, alcoholism, and Cocaine addiction show the higher influence in the mutated pathway networks based on the PageRank Algorithm where Dopaminergic Synapse system is also found within the same list in terms of Parkinson’s Disease pathogenicity.
Keywords
Parkinson's Disease , alpha-synuclein , aberrations
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The full text of this article is available to read as a PDF.
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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View the published article at Scientific Reports.
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See the published version of this preprint at Scientific Reports.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Ashmita Dey
Jadavpur University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Scientific Reports.
Version 1
Posted 05 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 15 Apr, 2021
Reviews received
Received 05 Apr, 2021
Reviewers agreed
On 02 Apr, 2021
Reviewers invited
Invitations sent on 02 Apr, 2021
Editor assigned
On 02 Apr, 2021
Editor invited
On 01 Apr, 2021
Submission checks complete
On 01 Apr, 2021
First submitted
On 30 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Scientific Reports.
Parkinson's Disease is a common neurodegenerative disease. The differential expression of alpha-synuclein within Lewy Bodies leads to this disease. Some missense mutations of alpha-synuclein may resultant in functional aberrations. In this study, our objective is to verify the functional adaptation due to early and late-onset mutation which can trigger or control the rate of alpha-synuclein aggregation. In this regard, we have proposed a computational model to study the difference and/or similarities among the Wild type alpha-synuclein and two mutations G51D and E46K which are responsible for slow and fast aggregation respectively. Evolutionary sequence space analysis is also performed in this experiment. Subsequently, a comparative study has been performed between structural information and sequence space outcomes. The study shows the structural variability among the selected subtypes. This information assists inter pathway modeling due to mutational aberrations. Based on the structural variability, we have identified the protein-protein interaction partners for each protein that helps to increase the robustness of the inter-pathway connectivity. As per the inter-pathway networks, drug addiction has clear impacts on both the mutations i.e., G51D-slow, and E46K-fast and can be considered as the reason for early-onset Parkinson’s Disease. Finally, three top pathways associated with drug addiction viz., Amphetamine addiction, alcoholism, and Cocaine addiction show the higher influence in the mutated pathway networks based on the PageRank Algorithm where Dopaminergic Synapse system is also found within the same list in terms of Parkinson’s Disease pathogenicity.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
The full text of this article is available to read as a PDF.
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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