Mutant SOD1-derived glial and neuronal restricted precursors as tools for understanding cell autonomy in ALS
Nicholas J. Maragakis, M.D.
Mahendra S. Rao, M.D., Ph.D.
National Institute on Aging,
ALS (Lou Gehrig’s disease) is a disease of the brain and spinal cord in which the nerve cells which send signals to muscles slowly die. Patients with ALS become progressively weak and ultimately die of respiratory failure. ALS affects adults of all ages and there is no an effective therapy for the disease. Why do motor neurons die in ALS? Many theories have been proposed, but emerging studies suggest that it is not only disease intrinsic to the motor neurons themselves, but also other cells of the brain—astrocytes, which contribute to the pathology seen in this disease. Astrocytes are responsible for maintaining the environment in which motor neurons function. Alterations in astrocytes may cause cell dysfunction and ultimately lead to motor neuron death.
What are the mechanisms involved in these astrocyte/motor neuron relationships? In order to study factors which may affect the biology of each of these cells both alone and when placed together, we propose to isolate both astrocyte and neuron stem cells from a mouse model of ALS. In doing so, we can study their interactions in a tissue culture dish. This allows us to rapidly study the pathways involved in astrocyte and motor neuron dysfunction in this disease.
