Figure 2.

Possible effects of TGFB on different tissues of amyotrophic lateral sclerosis (ALS) patients. At the pre-symptomatic stage, the decreased activation of the TGFB pathway reduces its neuroprotective activity, and, at the same time, increases excitotoxicity induced by glutamate, with a lesser uptake by astrocytes. At the symptomatic stage, TGFB levels are largely increased, giving rise to microglia activation, and neuromuscular junction (NMJ) dismantling, thus leading to atrophy of skeletal muscle fibers. ALS disease progression could be promoted by a chronically altered TGFB pathway. A, astrocyte; M, microglia; MN, motor neuron; SkMf, skeletal muscle fibers.