The more matured the society gets, the more growing the number of patients for neurodegenerative diseases such as Alzheimer's disease is. Neurodgenerative diseases grown up with aging are characterized by aggregate proteins cause neurodgeneration. TDP-43 is a nuclear protein that forms inclusion in the cytoplasm of neuronal and glial cells in about a half of the cases of frontotemproal lobar degeneration (FTLD) or most of the cases of amyotrophic lateral sclerosis (ALS). FTLD is classified into "Dementia", and ALS is classified into "Motor neuron disease", but the neuropathology of these diseases is overlapped in TDP-43 inclusion. Thus, FTLD characterized by TDP-43 inclusion (FTLD-TDP) and ALS is in the same spectrum neuropathologically, and these diseases are called "TDP-43 proteinopathy".

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1) TDP-43 gene mutations cause TDP-43 proteinopathy

2) TDP-43 has an essential role in maintenance of cells via RNA regulation etc.

3) The accumulation of TDP-43 in the cytoplasm negatively correlates with cognitive functions

These findings indicate that TDP-43 inclusion in the cytoplasm is not just result of the disease, but one of the cause of TDP-43 proteinopathy.

 

Our aim of the study is to reveal  "When, where or how TDP-43 accumulation in the cytoplasm starts".  Specially, we focus on the familial gene like Granulin , which causes TDP-43 proteinopathy .