Glial Reaction in Parkinson's Diseases: Inflammatory Activation Signaling of Glia as a Potential Therapeutic Target

Although the main cause of many neurodegenerative diseases is unknown, the glial reaction is considered to be a consequence of neuronal cell death in Alzheimer's disease, Parkinson's disease, and Huntington's disease. In Parkinson's disease, postmortem examination and experimental animal models exposed to neurotoxin reveals a dramatic loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. These glial cells can release deleterious compounds such as proinflammatory prostaglandins and cytokines, which may act by stimulating reactive oxygen species in glial cells, or which may exert a more direct effect on dopaminergic neurons by activating receptors that contain death domains involved in neuronal apoptosis. The anti-inflammatory drugs and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease. Elucidation of molecular mechanisms underlying intracellular signal transductions of glial activation will provide promising means of controlling neuroinflammation and the subsequent neurodegeneration.