The Mohamed Farah Lab studies axonal regeneration in the peripheral nervous system. We've found that genetic deletion and pharmacological inhibition of beta-amyloid cleaving enzyme (BACE1) markedly accelerate axonal regeneration in the injured peripheral nerves of mice. We postulate that accelerated nerve regeneration is due to blockade of BACE1 cleavage of two different BACE1 substrates. The two candidate substrates are the amyloid precursor protein (APP) in axons and tumor necrosis factor receptor 1 (TNFR1) on macrophages, which infiltrate injured nerves and clear the inhibitory myelin debris. In the coming years, we will systematically explore genetic manipulations of these two substrates in regard to accelerated axonal regeneration and rapid myelin debris removal seen in BACE1 KO mice. We also study axonal sprouting and regeneration in motor neuron disease models.