Role of the endoplasmic reticulum and of mitochondria in the Ca2+ metabolism of motor neurons.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Excitotoxicity is one of the mechanisms underlying this selective motor neuron death. Excitotoxicity is the pathological process that results from the overstimulation of the postsynaptic glutamate receptors, which leads ultimately to neuronal death. In this research project, we will investigate the intracellular systems that increase or diminish the calcium concentration in motor neurons. We will focus on the role of the endoplasmic reticulum and of mitochondria in the calcium metabolism as there are indications that these systems are compromised during the disease process and/or could predispose patients to ALS. In addition, we will search for strategies that counteract the disturbances in the calcium metabolism and that protect motor neurons. Using these strategies, we want to get a better understanding of the underlying mechanisms that cause the selective motor neuron death during ALS and we hope that we can contribute to the treatment of this dramatic and fatal neurodegenerative disorder.

Keywords:ALS, Amyotrophic lateral sclerosis, Excitotoxicity, Neurodegeneration, Calcium, Mitochondria, Endoplasmic reticulum, Motor neuron

Disciplines:Physiology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing