Apoptosis, glial cells and Parkinson's disease

The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. In Parkinson's disease, postmortem examination reveals that the loss of dopaminergic neurons in the substantia nigra is associated with massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, implying that toxic substances released by glial cells may be involved in neuronal degeneration. Glial cells can release various compounds, including pro-inflammatory cytokines. These substances may act on specific receptors, located on the dopaminergic neurons, that contain intracytoplasmic death domains and are involved in apoptosis. Alternatively, since cytokines are known to induce the expression of nitric oxide via the induction and activation of the low affinity IgE receptor CD23, the gradual release of nitric oxide from glial cells may account for the increased oxidative stress, protein nitration, altered iron homeostasis and blood vessel alterations reported in the disease. In turn, such cellular alterations may provoke the degeneration of dopaminergic neurons. The exact cascade of events leading to neuronal degeneration in Parkinson's disease is not known but may involve activation of proteases such as caspase-3, which are known effectors of the cascade of events leading to nerve cell death.