King's College London, Institute of Psychiatry
Endoplasmic reticulum-mitochondria interactions and Alzheimer's disease
Alzheimer's Research UK
Alzheimer's disease & other dementias
A wide number of cellular functions are perturbed in Alzheimers disease but it is not clear how so many apparently disparate functions are all damaged together. Recently, several studies have highlighted how damage to one particular cellular feature termed the endoplasmic reticulum (ER)-mitochondria axis might precipitate many Alzheimers disease type changes. ER and mitochondria are two structures within brain cells that perform different functions; ER is involved in making proteins and lipids, and mitochondria generate the energy for the cell. However, their proper functioning requires that they communicate with each other and this involves tethers that physically connect the two structures. In Alzheimers disease and related dementias, we and others have shown that ER-mitochondria communication is disrupted. Moreover, we have identified some of the protein tethers that connect ER with mitochondria and have shown that these are damaged in some forms of dementia. This project is to continue these studies. We aim to determine how the tethers and ER-mitochondria interactions are damaged in Alzheimers disease and to identify lead compounds that might correct this damage. We believe that our studies may reveal a new therapeutic target for treating Alzheimers disease.