Hallmarks of neurodegenerative disease: A systems pharmacology perspective.
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
17
07
2022
received:
20
04
2022
accepted:
19
07
2022
pubmed:
28
7
2022
medline:
18
11
2022
entrez:
27
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35894182
doi: 10.1002/psp4.12852
pmc: PMC9662204
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1399-1429Informations de copyright
© 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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