Fig. 1. Rat primary motor neurons are observed by the green signal. For a detailed description of the above image click here.

We grow rat neurons (cortical neurons or motor neurons) in dish in order to measure neurodegeneration. We infect our neurons with either an attenuated virus that expresses TDP-43 or a control protein (LacZ). When we do this, we see that TDP-43 kills the neurons while the neurons infected with the virus that expresses the control protein are unaffected (Fig.1). Our neuronal infection system serves as a platform for testing drugs that may prevent TDP-43 from killing the neurons. We have used our primary neuronal assay to show that small-molecule inhibitors of the PARP enzymes, PARP-1/2 and Tankyrase-1/2, reduce the neuronal death caused by TDP-43 (Fig.1). We now plan to use motor neurons made from human induced pluripotent stem cells.

References:

*McGurk L, Rifai O, and *Bonini NM. TDP-43, a protein central to amyotrophic lateral sclerosis, is destabilized by tankyrase-1 and -2. * denotes corresponding authors. J Cell Sci. 2020 May 14. online here

McGurk L, Mojsilovic-Petrovic J, Van Deerlin V, Shorter J, Kalb RG, Lee VM, Trojanowksi JQ, Lee EB and Bonini NM. (2018). Nuclear Poly(ADP-ribose) Activity is a Therapeutic Target in Amyotrophic Lateral Sclerosis. Acta Neuropathologica Communications 6:84. pdf