At present, this novel potential role played by TDP-43 in NPC and IBM diseases is being investigated and will be compared to the role played by this protein in ALS/FTD.ģ) in addition to aberrant aggregation, disease-asociated mutations in TDP-43 have also been found in a small number of patients. In addition, aberrant aggregation of TDP-43 was confirmed also to occur in patient IBM samples. Using NPC animal and IBM/NPC cellular models we have confirmed a mislocalization and aberrant expression of TDP-43 in the NPC models and in human autoptic tissues. We have recently expanded this list to include Niemann Pick C disease (NPC) and Inclusion Body Myositis (IBM). The reasons for these actions are currently being investigated to better understand disease origin and progression.Ģ) Aberrant TDP-43 pathology is not limited to the ALS/FTD spectrum but has been described to occur in a variety of other neurodegenerative diseases such as Alzheimer, Parkinisonism with dementia. Using cellular and animal models of disease we have identified several hnRNPs that can improve or worsen TDP-43 pathological functions both in loss-of-function and gain-of-function scenarios. Therefore, we have recently begun a project to study which cellular hnRNP proteins have the ability to affect TDP-43 functionality and aggregation in normal and diseased neurons. To address this issue, it is well known that TDP-43 co-operates with several other nuclear hnRNPs to regulate correct RNA processing. However, the effect of these aggregates on neuronal metabolism is still not clear. The following four major research projects are currently active in the Molecular Pathology lab:ġ) The presence of TDP-43 aggregates in the neurons of most patients affected by ALS/FTLD represents the most characteristic pathological feature of these diseases. Genetic disease caused by defective splicing. RNA-protein interactions. Defective RNA processing and neurodegeneration. Molecular Pathology NON-COMMUNICABLE DISEASES / Neurobiology Research Interests

Molecular pathology