Chapters authored
Contribution of Aberrant Astrocytes to Motor Neuron Damage and Death in the SOD1G93A Rat Experimental Model of ALS
Amyotrophic lateral sclerosis (ALS) is an incurable paralyzing disease characterized by motor neuron death and glial reactivity. Superoxide dismutase 1 (SOD1) are among the most frequent alterations found in around 15–20% of ALS inheritable forms. Mutant SOD1 murine models mimic main human ALS features and allow purposing that pathological mechanisms include defective communication between neural cells together with astrocyte preponderant roles in disease progression. Years ago, a subset of the most neurotoxic aberrant astrocytes (AbAs) was obtained from spinal cords of SOD1G93A rats. AbA cultures show an exponential growing yield since the early symptoms of the disease up to the terminal stages. In cultures, AbAs present unprecedented toxicity to motor neurons, increased proliferation, loss of mature astrocyte markers, as well as extreme ER stress and abundant extracellular matrix components. Strikingly, AbA phenotype seems to be changing along few passages suggesting its signaling and features may accompany disease progression. However, the link between main AbA features and their highest motor neuron toxicity is not yet completely understood. Here, we reviewed ALS underlying pathological mechanisms in association to AbA phenotype, to collaborate with identification of the most relevant processes that seem crucially involved in the triggering or maintenance of neurotoxicity.
Part of the book: Novel Aspects on Motor Neuron Disease