Figure 3. Hypothetical mechanisms of microtubule loss from neurons during neurodegenerative diseases.

Panel A shows the normal situation in the axon with individual microtubules displaying stable and labile domains. Panel B shows a scenario for potential loss of microtubule mass during neurodegeneration in which the stable domains are gradually destabilized, thus shifting individual microtubules to shorter stabile domains and longer labile domains that undergo greater depolymerization. Panel C shows enhanced depolymerization of the labile domains, without destabilization of the stable domains. Panel D shows microtubule loss due to increased microtubule severing. Severing in the labile domain results in complete depolymerization of the resulting labile microtubule fragments. Severing in the stable domain produces stable fragments with some accompanying depolymerization during the severing event. These three mechanistic possibilities could also apply to microtubule loss in dendrites.