Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Collection and Protein Interactome Construction
2.2. Cluster Analysis and Pathway Enrichment
2.3. Molecular Modelling of Crucial Cytosolic Proteins
2.4. Ligand Preparation and Molecular Docking
2.5. Molecular Dynamic Simulation
2.6. Patient Recruitment and Clinical Assessment
2.7. Gene Expression Profiling
2.8. Statistical Analysis
3. Results
3.1. Data Collection and Meta-Analysis of Cluster Proteins
3.2. Interactome and Pathway Enrichment Analysis
3.3. Molecular Docking and Molecular Dynamic Simulation
3.4. Gene Expression of DDO Gene in PD
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Istradefylline PD (n = 25) | Amantadine PD (n = 25) | Healthy Control (HC) (n = 25) | p-Value |
---|---|---|---|---|
Gender (Male/Female) | 13/12 | 8/17 | 17/8 | 0.527 |
Age (mean ± SD) | 56.51 ± 1.40 | 55.45 ± 1.81 | 51.18 ± 1.33 | 0.007 |
Age at onset (mean ± SD) | 48.46 ± 10.23 | 46.72 ± 11.68 | ||
Disease Duration Year (mean ± SD) | 6.92 ± 3.42 | 6.89 ± 3.14 | ||
UPDRS total (mean ± SD) | 42.45 ± 19.02 | 41.35 ± 18.02 | ||
UPDRS I | 6.57 ± 4.15 | 6.47 ± 3.05 | ||
UPDRS II | 11.09 ± 8.36 | 11.29 ± 7.58 | ||
UPDRS III | 23.57 ± 14.34 | 23.71 ± 13.14 | ||
UPDRS IV | 1.85 ± 5.48 | 1.91 ± 5.18 | ||
Hoehn and Yahr Scale | 2.12 ± 0.60 | 2.32 ± 0.50 |
Gene | Primer Sequence (5′->3′) | Ampliconic Size | |
---|---|---|---|
DDO | Forward Sequence | GGAGCTGAAATCTCTCACCTGG | 193 |
Reverse Sequence | CTCATGGACACAGCACGGAT | ||
GAPDH | Forward Sequence | TGTCATCAACGGAAAGGC | 183 |
Reverse Sequence | GCATCAGCAGAAGGAGCA |
Sl. No | Drug ID | Drug Name | DOCKING SCORE (kcal/mol) |
---|---|---|---|
1 | DB11757 | Istradefylline | −9.073 |
2 | DB06654 | Safinamide | −8.862 |
3 | DB00843 | Donepezil | −8.861 |
4 | DB00246 | Ziprasidone | −8.381 |
5 | DB06477 | Sumanirole | −8.256 |
6 | DB00494 | Entacapone | −8.153 |
7 | DB00490 | Buspirone | −8.074 |
8 | DB06454 | Sarizotan | −7.918 |
9 | DB01202 | Lavetriacetam | −7.879 |
10 | DB00323 | Tolcapone | −7.703 |
11 | DB00486 | Nabilone | −7.455 |
12 | DB00413 | Pramipexole | −7.246 |
13 | DB12551 | Idazoxan | −7.082 |
14 | DB06585 | Fipamezol | −7.025 |
15 | DB01367 | Rasagiline | −6.788 |
16 | DB00745 | Modafinil | −6.766 |
17 | DB00363 | Clozapine | −6.711 |
18 | DB05271 | Rotigotine | −6.679 |
19 | DB01235 | Levodopa | −6.601 |
20 | DB00571 | Propranol | −6.551 |
21 | DB06156 | Tesofensine | −6.517 |
22 | DB05814 | Gpi-1485 | −6.468 |
23 | DB01224 | Quetiapine | −6.333 |
24 | DB00472 | Fluoxetine | −6.31 |
25 | DB00268 | Ropinirole | −6.046 |
26 | DB00190 | Carbidopa | −6.025 |
27 | DB00674 | Galantamine | −6.012 |
28 | DB01183 | Naloxone | −5.886 |
29 | DB04982 | Talampanel | −5.768 |
30 | DB00714 | Apomorphine | −5.743 |
31 | DB01043 | Memantine | −5.605 |
32 | DB00989 | Rivastigmine | −5.486 |
33 | DB00334 | Olanzapine | −5.295 |
34 | DB01037 | Selegiline | −4.823 |
35 | DB00915 | Amantadine | −4.543 |
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Anirudhan, A.; Mahema, S.; Ahmad, S.F.; Emran, T.B.; Ahmed, S.S.S.J.; Paramasivam, P. Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity. Brain Sci. 2023, 13, 1551. https://doi.org/10.3390/brainsci13111551
Anirudhan A, Mahema S, Ahmad SF, Emran TB, Ahmed SSSJ, Paramasivam P. Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity. Brain Sciences. 2023; 13(11):1551. https://doi.org/10.3390/brainsci13111551
Chicago/Turabian StyleAnirudhan, Athira, S. Mahema, Sheikh F. Ahmad, Talha Bin Emran, Shiek S. S. J. Ahmed, and Prabu Paramasivam. 2023. "Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity" Brain Sciences 13, no. 11: 1551. https://doi.org/10.3390/brainsci13111551