Model scenarios for cell cycle re-entry in Alzheimer's disease
Summary: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Aberrant production and aggregation of amyloid beta (Aβ) peptide into plaques is a frequent feature of AD, but therapeutic approaches targeting Aβ accumulation fail to inhibit disease progression. The approved ch...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422200815X |
| _version_ | 1818204805735120896 |
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| author | Nishtha Pandey P.K. Vinod |
| author_facet | Nishtha Pandey P.K. Vinod |
| author_sort | Nishtha Pandey |
| collection | DOAJ |
| description | Summary: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Aberrant production and aggregation of amyloid beta (Aβ) peptide into plaques is a frequent feature of AD, but therapeutic approaches targeting Aβ accumulation fail to inhibit disease progression. The approved cholinesterase inhibitor drugs are symptomatic treatments. During human brain development, the progenitor cells differentiate into neurons and switch to a postmitotic state. However, cell cycle re-entry often precedes loss of neurons. We developed mathematical models of multiple routes leading to cell cycle re-entry in neurons that incorporate the crosstalk between cell cycle, neuronal, and apoptotic signaling mechanisms. We show that the integration of multiple feedback loops influences disease severity making the switch to pathological state irreversible. We observe that the transcriptional changes associated with this transition are also characteristics of the AD brain. We propose that targeting multiple arms of the feedback loop may bring about disease-modifying effects in AD. |
| first_indexed | 2024-12-12T03:47:05Z |
| format | Article |
| id | doaj.art-88426cecc28c4ef7990c7441dfc39208 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T03:47:05Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-88426cecc28c4ef7990c7441dfc392082022-12-22T00:39:29ZengElsevieriScience2589-00422022-07-01257104543Model scenarios for cell cycle re-entry in Alzheimer's diseaseNishtha Pandey0P.K. Vinod1Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032 IndiaCenter for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032 India; Corresponding authorSummary: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Aberrant production and aggregation of amyloid beta (Aβ) peptide into plaques is a frequent feature of AD, but therapeutic approaches targeting Aβ accumulation fail to inhibit disease progression. The approved cholinesterase inhibitor drugs are symptomatic treatments. During human brain development, the progenitor cells differentiate into neurons and switch to a postmitotic state. However, cell cycle re-entry often precedes loss of neurons. We developed mathematical models of multiple routes leading to cell cycle re-entry in neurons that incorporate the crosstalk between cell cycle, neuronal, and apoptotic signaling mechanisms. We show that the integration of multiple feedback loops influences disease severity making the switch to pathological state irreversible. We observe that the transcriptional changes associated with this transition are also characteristics of the AD brain. We propose that targeting multiple arms of the feedback loop may bring about disease-modifying effects in AD.http://www.sciencedirect.com/science/article/pii/S258900422200815XBioinformaticsBiological sciencesNeuroscienceSystems biologySystems neuroscience |
| spellingShingle | Nishtha Pandey P.K. Vinod Model scenarios for cell cycle re-entry in Alzheimer's disease iScience Bioinformatics Biological sciences Neuroscience Systems biology Systems neuroscience |
| title | Model scenarios for cell cycle re-entry in Alzheimer's disease |
| title_full | Model scenarios for cell cycle re-entry in Alzheimer's disease |
| title_fullStr | Model scenarios for cell cycle re-entry in Alzheimer's disease |
| title_full_unstemmed | Model scenarios for cell cycle re-entry in Alzheimer's disease |
| title_short | Model scenarios for cell cycle re-entry in Alzheimer's disease |
| title_sort | model scenarios for cell cycle re entry in alzheimer s disease |
| topic | Bioinformatics Biological sciences Neuroscience Systems biology Systems neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S258900422200815X |
| work_keys_str_mv | AT nishthapandey modelscenariosforcellcyclereentryinalzheimersdisease AT pkvinod modelscenariosforcellcyclereentryinalzheimersdisease |