Dr P. Fratta

Defining TDP43 dependant RNA changes

(with Abraham Acevedo-Arozena)

Aim: to identify changes in RNA metabolism due to TDP43 loss and gain of function in mammalian CNS.

Neuronal TDP43 cytoplasmic inclusions are present in >98% of ALS post-mortem cases and represent a major hallmark of the disease. They are intriguingly accompanied by nuclear depletion of TDP43, raising the question whether there is a nuclear loss of function in RNA processing.

We are currently using two novel models carrying point mutations in TDP43 which cause widespread changes in RNA metabolism, to better understand the biology of TDP43 and its function in the CNS.

We also use muscle biopsy material, where TDP43 shows pathological aggregation, to study RNA profiles occurring in patients.