Fig. 4.

MT bundle defects as cause or consequence of axon decay. 1) Disease-inducing mutations/conditions can affect a MT bundle regulator (e.g. dystonin [90]), thus causing MT bundle defects first which, in turn, can trigger axon decay. 2) Disease-inducing mutations/conditions can affect systemic factors which, in turn cause MT bundle defects as an intermediate causative step in the cascade leading to axon decay (e.g. axonal transport fails, leading to MT bundle defects which then contribute to axon decay, as is the case in Alzheimer's disease or ALS [302, 406, 407]); this may occur even if MT regulators are affected, but these regulators mainly act in the cell body (e.g. dysregulation of the Golgi [408]). 3) MT bundle deterioration may be a mere consequence of axon decay, although this case will be difficult to disentangle from option 2, since MT bundle disintegration and axonal disassembly may occur in parallel, as observed in developmental or injury-induced axon degeneration [409–411]). All MT-related phenotypes in this graph are indicated with a frame