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.
Lab Website: Mohamed Farah Lab
Tasnim A , Rammelkamp Z, Slusher AB, Krystyna Wozniak C, Slusher BS, Farah MH. Paclitaxel Causes Degeneration of both Central and Peripheral Axon Branches of Dorsal Root Ganglia in Mice. Accepted April 5, 2016 in MBC Neuroscience
Liu L, Fissel JA, Tasnim A, Borzan J, Gocke A, Calabresi, PA, Farah MH. Increased TNFR1 expression and signaling in injured peripheral nerves of mice with reduced BACE1 activity. Neurobiology of Disease. In press doi: 10.1016/j.nbd.2016.04.002
Tallon C, Russell KA, Sakhalkar S, Andrapallayal A, Farah MH. Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice. Neuroscience. 2016 Jan 15;312:179-89. doi: 10.1016/j.neuroscience.2015.11.018. Epub 2015 Nov 18.
Dali C í, Barton NW, Farah MH, Moldovan M, Månsson. J, Nair N, Dunø M, Risom L, Cao H, Pan L, Sellos-Moura M, Corse AM, and Krarup, C. Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy. Ann Clin Transl Neurol. 2015 May;2(5):518-33.
Morrison BM , Tsingalia A, Vidensky S, Lee Y, Jin L, Farah MH, Lengacher S, Pellerin L, Magistretti PJ, Rothstein JD. Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush. Exp Neurol . Exp Neurol. 2015 Jan;263:325-38.
Farah MH. Robust regeneration after peripheral nerve injury.
Patent # 20130108645 | 2013