Jamming of phosphorylated τ-proteins leads to the formation of τ -tangles creating a feedback of disruption in cellular transport machinery
While many of the biological aspects that contribute to the formation of Aβ plaques are well addressed at the intra- and inter-cellular level in short timescales, an understanding of how Aβ fibrillization leads to the formation of τ-tangles in the intra-neuronal domain at a relatively longer timescale in spite of the presence of mechanisms dedicated to Aβ clearance, is still lacking. Furthermore, no existing mathematical model integrates the impact of amyloid β (Aβ) fibrillization as emanated from the disruption of APP homeostasis to predict disease progression due to the formation of τ-tangles after the phosphorylation of τ-proteins which are otherwise bound with the microtubules. Using an agent-based simulation of asymmetric exclusion processes along the microtubules, we show how the jamming of the phosphorylated τ-proteins is initiated as a consequence of disruption of cellular transport due to blocking of extra-cellular matrix by the amyloid plaques. Our results are also suggestive of a vicious cycle of the disruption in transport machinery and damage to the neuron.
Martin Korte (TU Braunschweig)
- Systems Immunology- Prof. Dr. Michael Meyer-Hermann