Neuronal microtubules: when the MAP is the roadblock

Abstract

Recent studies shed new light on a potential cascade of events by which neurological diseases such as Alzheimer's lead to axonal degeneration. In this model, the pathology starts with an elevation in microtubule-associated proteins (MAPs) such as tau. This renders the microtubules less accessible to motor proteins, which impairs their capacity to sustain anterograde axonal transport of proteins and organelles. In response, the neuron hyperphosphorylates tau so that it dissociates from the microtubules. Unfortunately, the hyperphosphorylated tau forms abnormal filaments that are deleterious to the axon, and the tau-depleted microtubules become highly sensitive to microtubule-severing proteins such as katanin.