We have identified that TDP-43 is imported into the nucleus via the Karyopheirn beta 1 pathway and that knockdown of members of the pathway can lead to cytoplasmic accumulation of TDP-43. We have also observed that one of the members of the pathway, CAS (cell apoptosis susceptibility protein) is greatly reduced in the post-mortem brain tissue of patients who had FTLD, which may be one of the reasons for cytoplasmic TDP-43 accumulation in this disease. This finding suggests that the disturbance in the nuclear transport of TDP-43 could be one of the root causes of TDP-43 proteinopathies.
COBISS.SI-ID: 23645223
X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer's disease.
COBISS.SI-ID: 23644967