Sneppen2009 - Modeling proteasome dynamics in Parkinson's disease

Sneppen2009 - Modeling proteasome dynamics in
Parkinson's disease

This model is described in the article:

Modeling proteasome dynamics
in Parkinson's disease.

Sneppen K, Lizana L, Jensen MH,
Pigolotti S, Otzen D.
Phys Biol 2009; 6(3): 036005
Abstract:

In Parkinson's disease (PD), there is evidence that
alpha-synuclein (alphaSN) aggregation is coupled to
dysfunctional or overburdened protein quality control systems,
in particular the ubiquitin-proteasome system. Here, we develop
a simple dynamical model for the on-going conflict between
alphaSN aggregation and the maintenance of a functional
proteasome in the healthy cell, based on the premise that
proteasomal activity can be titrated out by mature alphaSN
fibrils and their protofilament precursors. In the presence of
excess proteasomes the cell easily maintains homeostasis.
However, when the ratio between the available proteasome and
the alphaSN protofilaments is reduced below a threshold level,
we predict a collapse of homeostasis and onset of oscillations
in the proteasome concentration. Depleted proteasome opens for
accumulation of oligomers. Our analysis suggests that the onset
of PD is associated with a proteasome population that becomes
occupied in periodic degradation of aggregates. This behavior
is found to be the general state of a proteasome/chaperone
system under pressure, and suggests new interpretations of
other diseases where protein aggregation could stress elements
of the protein quality control system.

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