Astrocytes and therapeutics for Parkinson's disease.
Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in amyotrophic lateral sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context-dependent dual role of astrocytes has also been documented in experimental models of Parkinson's disease. The present review addresses these studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in Parkinson's disease, and in particular examines how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release proinflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of Parkinson's disease constitute an exciting development with promising novel therapeutic targets.
Rappold
Phillip M
PM
Department of Neurology, Center for Translational Neuromedicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Tieu
Kim
K
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009410:Nerve Degeneration / Q000209:etiology / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*
D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D005978:Glutathione