Calcium homeostasis and excitotoxicity



The role of mitochondria and ER during neuronal and glial Ca2+ homeostasis disruption

Calcium homeostasis disruption is a hallmark of most CNS diseases and therefore a research field of high therapeutic interest. In particular, overactivation of glutamate ionotropic receptors produces a cytosolic calcium overload that causes excitotoxic death of neurons and oligodendrocytes and contributes to acute and neurodegenerative disorders such as stroke and Alzheimer´s disease. As a part of the Laboratoy of Neurobiology, we are focused on the role of both mitochondria and endoplasmic reticulum (ER), which are critically involved in these pathological conditions. These organelles are the most important cytoplasmic Ca2+ stores inside the cell and therefore directly impact Ca2+ homeostasis. In addition, Ca2+ homeostasis disruption itself induces ER stress and mitochondrial dysfunction, leading to neuronal and glial cell loss. Using live-cell imaging and molecular biology techniques we study how (i) mitochondrial Ca2+ dynamics and function and (ii) ER stress and related UPR (unfolded protein response) contribute to excitotoxicity, and whether they can be modulated to provide neuroprotection.

Deconvolved confocal micrograph of astrocytic mitochondria (Cytochrome C labelling)  

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