Skip to main content
. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Acta Neuropathol. 2014 Dec 31;129(4):469–491. doi: 10.1007/s00401-014-1380-1

Figure 1. TDP-43 Mediated Neurodegeneration in FTLD-TDP/ALS.

Figure 1

Pathological TDP-43 translocation from the nucleus (red) to the cytoplasmic compartment occurs in sporadic disease and hereditary cases with C9orf72, TARDBP, GRN, and VCP mutations. VCP mutation cases also have intranuclear TDP-43 inclusions (not shown). C9orf72 mutation is associated with additional RNA foci in the nucleus (green) and cytoplasmic di-peptide repeat inclusions (blue), but the specific association with neurodegeneration is currently unclear. Neuron-to-neuron transmission is the likely mechanism for the non-random pattern of spread of neurodegeneration. These processes are linked to RNA dysfunction and abnormal proteostasis, ultimately leading to neuronal cell loss and/or muscle denervation from lower motor neuron loss. Drug-development efforts to slow or halt this process may provide novel disease modifying therapies in the future.