Matthew J. Winton

TL;DR: FTLD-U/ALS pathogenesis may be linked mechanistically to deleterious perturbations of nuclear trafficking and solubility of TDP-43, as well as to mutants with defective nuclear localization or nuclear export signals.

TL;DR: The data suggest that perturbation of endogenous nuclear TDP-43 results in loss of normal T DP-43 function(s) and gene regulatory pathways, culminating in degeneration of selectively vulnerable affected neurons.

TL;DR: The hypothesis that the generation of TDP-43 CTFs is an important step in the pathogenesis of FTLD-U and ALS is supported and the specific cleavage site(s) are identified, Arg208, of a pathological TTP purified from FT LD-U brains and expression recapitulates key biochemical features of pathological T DP-43 proteinopathy are shown.

TL;DR: Results show that degeneration associated with VCP mutations is mediated in part by toxic gain of function of TDP-43 in the cytoplasm, which is likely relevant to the pathogenic mechanism of a broad array of T DP-43 proteinopathies, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

TL;DR: Results indicate that application of a Rho antagonist at the cell body is neuroprotective and overcomes growth inhibition but does not fully prime RGCs for active growth.