Abstract

Neuroinflammation is a hallmark of many neurodegenerative diseases such as Alzheimer’s and Parkinson’s. In the brain, inflammation is most often caused by a special type of brain immune cell called microglia. Depending on the type of damage the brain has sustained, the microglia can either enter into a pro-inflammatory state known as M1, or an anti-inflammatory state known as M2. In neurodegenerative diseases, either state can become chronic. One way this could happen is through Mitochondrial Dysfunction Associated Senescence (MiDAS), a form of cellular senescence arising from a feedback loop in which mitochondria stay in a hyperfused network for too long and cannot produce a sufficient amount of ATP to exit hyperfusion. The present study proposes a Boolean model of the MiDAS feedback loop, an in silico method that investigates the cellular conditions under which MiDAS can occur. The results show that MiDAS does not occur during a moderate amount of DNA damage, as well as a normal G1/S phase transition. MiDAS does occur from a high amount of DNA damage perpetuated by an abundance of Reactive Oxygen Species (ROS) but can be rescued by the knockdown or overexpression of several proteins and molecules involved in MiDAS. These results indicate several possibilities of further study that could ultimately lead to better treatments for neuroinflammation.

Advisor

Regan, Erzsébet

Department

Neuroscience

Disciplines

Molecular and Cellular Neuroscience | Nervous System Diseases | Systems Biology | Systems Neuroscience

Keywords

Mitochondria, Neurodegenerative Diseases, Microglia, Boolean Modeling, Neuroscience

Publication Date

2023

Degree Granted

Bachelor of Arts

Document Type

Senior Independent Study Thesis

Additional Files
Fleig_MIDAS.dmms (59 kB)
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© Copyright 2023 Katherine H. Fleig