La sclérose latérale amyotrophique: une maladie progressive des neurones moteurs et de la microglie

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that produces progressive muscle weakness and wasting of the limb and bulbar muscles and eventual death from respiratory failure in most cases. The cell death process in amyotrophic lateral sclerosis is relatively selective for lower motoneuron groups in the spinal cord and brain stem, and for upper motor neurons in the motor cortex. The precise molecular pathways leading to motor neuron injury and cell death in amyotrophic lateral sclerosis remain incompletely understood. A body of evidence has emerged to indicate that the neuronal injury in amyotrophic lateral sclerosis reflects a complex interaction between genetic factors, imbalance of the glutamatergic transmitter system and oxidative stress. There is also emerging evidence that motor neurons may die by a programmed cell death pathway and that microglia may release factors that are toxic for the neurons. In relation to several of these factors, there are cell-specific features which may render motoneurons susceptible to injury. This article discusses the main areas of investigation and reviews the findings.