This publication reports mutations of TDP-43 associated with amyotrophic lateral sclerosis (ALS). TDP-43 is a nuclear protein, whose main known function is in metabolism of RNA (splicinng and expression of mRNA, miRNA biogenesis, etc.). This finding suggests the increasing importance of RNA metabolism in neurodegenerative diseases.
COBISS.SI-ID: 24798681
This publication reports mutations of FUS associated with amyotrophic lateral sclerosis (ALS). FUS is a nuclear protein, whose main known function is in metabolism of RNA (splicinng and expression of mRNA, miRNA biogenesis, etc.). This finding suggests the increasing importance of RNA metabolism in neurodegenerative diseases, especially as TDP-43, another ALS associated protein has simillar characteristics.
COBISS.SI-ID: 22877479
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
Routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer's disease. X11ß is a neuronal adaptor protein that binds to the intracellular domain of APP. We report that X11ß-mediated reduction in cerebral Aß is associated with normalisation of cognition in aged APPswe Tg2576 transgenic mice. Overexpression of X11ß itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11ß function represents a therapeutic target for Aß-mediated neuronal dysfunction in Alzheimer's disease.
COBISS.SI-ID: 22913319