Modeling the growth of cytosolic TDP-43 inclusion bodies and accumulated neurotoxicity of misfolded oligomers in neurons - PubMed
6 hours ago
- #TDP-43
- #mathematical modeling
- #neurotoxicity
- Introduction of a mathematical model for TDP-43 inclusion body growth in neuron soma.
- Model includes parameters for neurotoxicity from misfolded TDP-43 oligomers.
- Equations calculate concentrations of TDP-43 monomers, dimers, free oligomers, and inclusion body deposits.
- Simulation predicts inclusion body size and neurotoxicity accumulation.
- Approximate solution for dysfunctional protein degradation shows inclusion body radius grows with cube root of time and neurotoxicity increases linearly.
- First study to model TDP-43 inclusion body size over time and introduce accumulated neurotoxicity concept.
- Sensitivity analysis shows inclusion body radius and neurotoxicity become independent of kinetic constants at large timescales.
- Numerical solution for finite half-lives indicates long-term behavior depends on kinetic constants.