Parkinson’s disease is marked by the progressive loss of dopaminergic neurons and the prion-like spread of misfolded α-synuclein. This study presents a computational framework simulating α-synuclein propagation and neuron death within a simplified substantia nigra model. Cellular automata were used to model local transmission, oxidative stress, and cumulative toxicity, while Braak-stage-informed parameters guided regional progression. The simulation explores how mitochondrial stress thresholds and α-synuclein seeding density alter neurodegeneration patterns. This model provides a visualizable, modular tool to test hypotheses on disease progression and therapeutic timing.
References
[1]
Van Maele-Fabry, G., Hoet, P., Vilain, F. and Lison, D. (2012) Occupational Expo-sure to Pesticides and Parkinson’s Disease: A Systematic Review and Meta-Analysis. Occupational and Environmental Medicine, 69, 529-535.
[2]
Subramaniam, S.R. and Chesselet, M. (2013) Mitochondrial Dysfunction and Oxidative Stress in Parkinson’s Disease. Progress in Neurobiology, 106, 17-32. https://doi.org/10.1016/j.pneurobio.2013.04.004
[3]
Cuddy, L.K., Winick-Ng, W. and Rylett, R.J. (2019) Regulation of Oxidative Stress in Parkinson’s Disease. Brain, 142, 1400-1415.
[4]
Sian‐Hülsmann, J., Mandel, S., Youdim, M.B.H. and Riederer, P. (2011) The Relevance of Iron in the Pathogenesis of Parkinson’s Disease. Journal of Neurochemistry, 118, 939-957. https://doi.org/10.1111/j.1471-4159.2010.07132.x
[5]
Armstrong, M.J. and Okun, M.S. (2020) Diagnosis and Treatment of Parkinson Disease. JAMA, 323, 548-560. https://doi.org/10.1001/jama.2019.22360
[6]
Uemura, N. and Oka, A. (2021) Pathophysiological Mechanisms of α-Synuclein Spread in Parkinson’s Disease. Neurobiology of Disease, 153, Article 105327.
[7]
Lee, H., Suk, J., Bae, E. and Lee, S. (2008) Clearance and Deposition of Extracellular Α-Synuclein Aggregates in Microglia. Biochemical and Biophysical Research Communications, 372, 423-428. https://doi.org/10.1016/j.bbrc.2008.05.045
[8]
Holmqvist, S., Chutna, O., Bousset, L., Aldrin-Kirk, P., Li, W., Björklund, T., et al. (2014) Direct Evidence of Parkinson Pathology Spread from the Gastrointestinal Tract to the Brain in Rats. Acta Neuropathologica, 128, 805-820. https://doi.org/10.1007/s00401-014-1343-6
[9]
Lafrenaye, A.D. and Simard, J.M. (2019) Immune System Contributions to Secondary Injury and Neurodegeneration in Parkinson’s Disease. Frontiers in Aging Neuroscience, 11, 44.
[10]
Bousset, L., Pieri, L., Ruiz-Arlandis, G., Gath, J., Jensen, P.H., Habenstein, B., et al. (2013) Structural and Functional Characterization of Two Alpha-Synuclein Strains. Nature Communications, 4, Article No. 2575. https://doi.org/10.1038/ncomms3575
[11]
Johnson, M.E., Stecher, B., Labrie, V., Brundin, L. and Brundin, P. (2019) Triggers, Facilitators, and Aggravators: Redefining Parkinson’s Disease Pathogenesis. Trends in Neurosciences, 42, 4-13. https://doi.org/10.1016/j.tins.2018.09.007
[12]
Zhang, X., Jin, Q., Jin, Y., et al. (2021) Anti-Oxidative Stress and Anti-Apoptosis Roles of Metformin in Neurodegeneration. Aging and Disease, 12, 1189-1203.
[13]
Braak, H. and Del Tredici, K. (2009) Neuroanatomy and Pathology of Sporadic Par-kinson’s Disease. Advances in Anatomy, Embryology and Cell Biology, 201, 1-119.
[14]
Del Tredici, K. and Braak, H. (2016) Review: Sporadic Parkinson’s Disease: Development and Distribution Ofα‐synuclein Pathology. Neuropathology and Applied Neurobiology, 42, 33-50. https://doi.org/10.1111/nan.12298
[15]
Topol, E. (2022) The Convergence of Health Care and Technology in Neurodegeneration. The Lancet Digital Health, 4, e239-e241.
[16]
Singh, N., Pillay, V. and Choonara, Y.E. (2022) Nanomedicine Advances in Parkin-son’s Disease: Targeted Delivery across Blood-Brain Barrier. International Journal of Molecular Sciences, 23, 1497.