Hallmarks of neurodegenerative disease: A systems pharmacology perspective
Abstract Age‐related central neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are a rising public health concern and have been plagued by repeated drug development failures. The complex nature and poor mechanistic understanding of the etiology of neurodegenerative d...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12852 |
| _version_ | 1797989057661239296 |
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| author | Peter Bloomingdale Tatiana Karelina Vidya Ramakrishnan Suruchi Bakshi Florence Véronneau‐Veilleux Matthew Moye Kazutaka Sekiguchi Guy Meno‐Tetang Aparna Mohan R. Maithreye Veena A. Thomas Frank Gibbons Antonio Cabal Jean‐Marie Bouteiller Hugo Geerts |
| author_facet | Peter Bloomingdale Tatiana Karelina Vidya Ramakrishnan Suruchi Bakshi Florence Véronneau‐Veilleux Matthew Moye Kazutaka Sekiguchi Guy Meno‐Tetang Aparna Mohan R. Maithreye Veena A. Thomas Frank Gibbons Antonio Cabal Jean‐Marie Bouteiller Hugo Geerts |
| author_sort | Peter Bloomingdale |
| collection | DOAJ |
| description | Abstract Age‐related central neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are a rising public health concern and have been plagued by repeated drug development failures. The complex nature and poor mechanistic understanding of the etiology of neurodegenerative diseases has hindered the discovery and development of effective disease‐modifying therapeutics. Quantitative systems pharmacology models of neurodegeneration diseases may be useful tools to enhance the understanding of pharmacological intervention strategies and to reduce drug attrition rates. Due to the similarities in pathophysiological mechanisms across neurodegenerative diseases, especially at the cellular and molecular levels, we envision the possibility of structural components that are conserved across models of neurodegenerative diseases. Conserved structural submodels can be viewed as building blocks that are pieced together alongside unique disease components to construct quantitative systems pharmacology (QSP) models of neurodegenerative diseases. Model parameterization would likely be different between the different types of neurodegenerative diseases as well as individual patients. Formulating our mechanistic understanding of neurodegenerative pathophysiology as a mathematical model could aid in the identification and prioritization of drug targets and combinatorial treatment strategies, evaluate the role of patient characteristics on disease progression and therapeutic response, and serve as a central repository of knowledge. Here, we provide a background on neurodegenerative diseases, highlight hallmarks of neurodegeneration, and summarize previous QSP models of neurodegenerative diseases. |
| first_indexed | 2024-04-11T08:14:11Z |
| format | Article |
| id | doaj.art-d627f76b245a4babb9f9c159235ee333 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-04-11T08:14:11Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-d627f76b245a4babb9f9c159235ee3332022-12-22T04:35:14ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062022-11-0111111399142910.1002/psp4.12852Hallmarks of neurodegenerative disease: A systems pharmacology perspectivePeter Bloomingdale0Tatiana Karelina1Vidya Ramakrishnan2Suruchi Bakshi3Florence Véronneau‐Veilleux4Matthew Moye5Kazutaka Sekiguchi6Guy Meno‐Tetang7Aparna Mohan8R. Maithreye9Veena A. Thomas10Frank Gibbons11Antonio Cabal12Jean‐Marie Bouteiller13Hugo Geerts14Quantitative Pharmacology and Pharmacometrics Merck & Co., Inc. Boston Massachusetts USAInSysBio Moscow RussiaClinical Pharmacology Genentech, Inc. South San Francisco California USACertara QSP Oss The NetherlandsFaculté de Pharmacie University of Montreal Montreal Quebec CanadaQuantitative Pharmacology and Pharmacometrics Merck & Co., Inc. Boston Massachusetts USAShionogi & Co., Ltd. Osaka JapanNeuroscience, Biopharmaceuticals R&D AstraZeneca Cambridge UKVantage Research Chennai Tamil Nadu IndiaVantage Research Chennai Tamil Nadu IndiaAmgen South San Francisco California USAClinical Pharmacology and Pharmacometrics Biogen Cambridge Massachusetts USAEisai Nutley New Jersey USACenter for Neural Engineering Department of Biomedical Engineering at the Viterbi School of Engineering Los Angeles California USACertara QSP Oss The NetherlandsAbstract Age‐related central neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are a rising public health concern and have been plagued by repeated drug development failures. The complex nature and poor mechanistic understanding of the etiology of neurodegenerative diseases has hindered the discovery and development of effective disease‐modifying therapeutics. Quantitative systems pharmacology models of neurodegeneration diseases may be useful tools to enhance the understanding of pharmacological intervention strategies and to reduce drug attrition rates. Due to the similarities in pathophysiological mechanisms across neurodegenerative diseases, especially at the cellular and molecular levels, we envision the possibility of structural components that are conserved across models of neurodegenerative diseases. Conserved structural submodels can be viewed as building blocks that are pieced together alongside unique disease components to construct quantitative systems pharmacology (QSP) models of neurodegenerative diseases. Model parameterization would likely be different between the different types of neurodegenerative diseases as well as individual patients. Formulating our mechanistic understanding of neurodegenerative pathophysiology as a mathematical model could aid in the identification and prioritization of drug targets and combinatorial treatment strategies, evaluate the role of patient characteristics on disease progression and therapeutic response, and serve as a central repository of knowledge. Here, we provide a background on neurodegenerative diseases, highlight hallmarks of neurodegeneration, and summarize previous QSP models of neurodegenerative diseases.https://doi.org/10.1002/psp4.12852 |
| spellingShingle | Peter Bloomingdale Tatiana Karelina Vidya Ramakrishnan Suruchi Bakshi Florence Véronneau‐Veilleux Matthew Moye Kazutaka Sekiguchi Guy Meno‐Tetang Aparna Mohan R. Maithreye Veena A. Thomas Frank Gibbons Antonio Cabal Jean‐Marie Bouteiller Hugo Geerts Hallmarks of neurodegenerative disease: A systems pharmacology perspective CPT: Pharmacometrics & Systems Pharmacology |
| title | Hallmarks of neurodegenerative disease: A systems pharmacology perspective |
| title_full | Hallmarks of neurodegenerative disease: A systems pharmacology perspective |
| title_fullStr | Hallmarks of neurodegenerative disease: A systems pharmacology perspective |
| title_full_unstemmed | Hallmarks of neurodegenerative disease: A systems pharmacology perspective |
| title_short | Hallmarks of neurodegenerative disease: A systems pharmacology perspective |
| title_sort | hallmarks of neurodegenerative disease a systems pharmacology perspective |
| url | https://doi.org/10.1002/psp4.12852 |
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