Several neurological disorders are associated with the aggregation of aberrant proteins, often localized in intracellular organelles such as the endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field reactions and three dimensional Monte carlo simulations of diffusion-limited aggregation of linear polymers in a confined space, representing the endoplasmic reticulum. By tuning the rates of protein production and degradation, we show that the system undergoes a non-equilibrium phase transition from a physiological phase with little or no polymer accumulation to a pathological phase characterized by persistent polymerization. A combination of external factors accumulating during the lifetime of a patient can thus slightly modify the phase transition control parameters, tipping the balance from a long symptomless lag phase to an accelerated pathological development. The model can be successfully used to interpret experimental data on amyloid-Î 2 clearance from the central nervous system.
|Titolo:||Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition|
|Parole Chiave:||MOLECULAR-DYNAMICS SIMULATIONS; DEMENTIA FENIB; ALZHEIMERS-DISEASE; FORMS POLYMERS; LUNG-DISEASE; NEUROSERPIN; PEPTIDES; SERPINOPATHIES; DEGRADATION; PROTEASOMES|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore FIS/03 - Fisica della Materia
|Data di pubblicazione:||11-apr-2014|
|Digital Object Identifier (DOI):||10.1038/ncomms4620|
|Appare nelle tipologie:||01 - Articolo su periodico|