Mathematical Biology Models of Parkinson's Disease

Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine (DA) deficiency in the brain. Treatments aimed at DA restorati...

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Published inCPT: pharmacometrics and systems pharmacology Vol. 8; no. 2; pp. 77 - 86
Main Authors Bakshi, Suruchi, Chelliah, Vijayalakshmi, Chen, Chao, Graaf, Piet H.
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.02.2019
John Wiley and Sons Inc
Subjects
Alzheimer's disease
Brain
Clinical trials
Dopamine
Feedback
Metabolism
Nitrogen
NMR
Nuclear magnetic resonance
Ordinary differential equations
Oxidative stress
Parkinson's disease
Pathogenesis
Polymerization
Review
Reviews
System theory
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Abstract Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine (DA) deficiency in the brain. Treatments aimed at DA restoration provide symptomatic relief, however, no disease modifying treatments are available, and PD remains incurable to date. Mathematical modeling can help understand such complex multifactorial neurological diseases. We review mathematical modeling efforts in PD with a focus on mechanistic models of pathogenic processes. We consider models of α‐synuclein (Asyn) aggregation, feedbacks among Asyn, DA, and mitochondria and proteolytic systems, as well as pathology propagation through the brain. We hope that critical understanding of existing literature will pave the way to the development of quantitative systems pharmacology models to aid PD drug discovery and development.
AbstractList Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine (DA) deficiency in the brain. Treatments aimed at DA restoration provide symptomatic relief, however, no disease modifying treatments are available, and PD remains incurable to date. Mathematical modeling can help understand such complex multifactorial neurological diseases. We review mathematical modeling efforts in PD with a focus on mechanistic models of pathogenic processes. We consider models of α‐synuclein (Asyn) aggregation, feedbacks among Asyn, DA, and mitochondria and proteolytic systems, as well as pathology propagation through the brain. We hope that critical understanding of existing literature will pave the way to the development of quantitative systems pharmacology models to aid PD drug discovery and development.
Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio-economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine (DA) deficiency in the brain. Treatments aimed at DA restoration provide symptomatic relief, however, no disease modifying treatments are available, and PD remains incurable to date. Mathematical modeling can help understand such complex multifactorial neurological diseases. We review mathematical modeling efforts in PD with a focus on mechanistic models of pathogenic processes. We consider models of α-synuclein (Asyn) aggregation, feedbacks among Asyn, DA, and mitochondria and proteolytic systems, as well as pathology propagation through the brain. We hope that critical understanding of existing literature will pave the way to the development of quantitative systems pharmacology models to aid PD drug discovery and development.Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio-economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine (DA) deficiency in the brain. Treatments aimed at DA restoration provide symptomatic relief, however, no disease modifying treatments are available, and PD remains incurable to date. Mathematical modeling can help understand such complex multifactorial neurological diseases. We review mathematical modeling efforts in PD with a focus on mechanistic models of pathogenic processes. We consider models of α-synuclein (Asyn) aggregation, feedbacks among Asyn, DA, and mitochondria and proteolytic systems, as well as pathology propagation through the brain. We hope that critical understanding of existing literature will pave the way to the development of quantitative systems pharmacology models to aid PD drug discovery and development.
Parkinsons disease ( PD ) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging, environmental, and genetic factors contribute to neurodegeneration and dopamine ( DA ) deficiency in the brain. Treatments aimed at DA restoration provide symptomatic relief, however, no disease modifying treatments are available, and PD remains incurable to date. Mathematical modeling can help understand such complex multifactorial neurological diseases. We review mathematical modeling efforts in PD with a focus on mechanistic models of pathogenic processes. We consider models of α‐synuclein (Asyn) aggregation, feedbacks among Asyn, DA , and mitochondria and proteolytic systems, as well as pathology propagation through the brain. We hope that critical understanding of existing literature will pave the way to the development of quantitative systems pharmacology models to aid PD drug discovery and development.
Author Graaf, Piet H.
Bakshi, Suruchi
Chelliah, Vijayalakshmi
Chen, Chao
AuthorAffiliation 2 Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research (LACDR) Leiden University Leiden The Netherlands
5 Certara QSP Canterbury
4 Clinical Pharmacology Modelling & Simulation GlaxoSmithKline Uxbridge UK
3 Certara QSP Sheffield UK
1 Certara QSP Breda The Netherlands
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– ident: e_1_2_7_13_1
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  doi: 10.1016/S0022-2836(62)80112-0
– ident: e_1_2_7_71_1
  doi: 10.1103/PhysRevE.91.042111
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Snippet Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging,...
Parkinsons disease ( PD ) is a progressive neurodegenerative disease with substantial and growing socio‐economic burden. In this multifactorial disease, aging,...
Parkinsons disease (PD) is a progressive neurodegenerative disease with substantial and growing socio-economic burden. In this multifactorial disease, aging,...
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SubjectTerms Alzheimer's disease
Brain
Clinical trials
Dopamine
Feedback
Metabolism
Nitrogen
NMR
Nuclear magnetic resonance
Ordinary differential equations
Oxidative stress
Parkinson's disease
Pathogenesis
Polymerization
Review
Reviews
System theory
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Title Mathematical Biology Models of Parkinson's Disease
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpsp4.12362
https://www.ncbi.nlm.nih.gov/pubmed/30358157
https://www.proquest.com/docview/2266279861
https://www.proquest.com/docview/2125298323
https://pubmed.ncbi.nlm.nih.gov/PMC6389348
Volume 8
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