Pathological glial reactions in neurodegenerative disorders: prospects for future therapeutics.
Pathological activation of the immune-competent glial cells is an obligatory event in neurodegenerative diseases. The secondary recruitment of astrocytes, resulting from an upgraded microglial activation, represents a critical point. Reactive astrocytes have to give up physiologically important functions (control of extracellular homeostasis and of synaptic transmission) and build a synergistic alliance with microglia in promoting oxidative, excitotoxic and beta-amyloid-induced neuronal damage. Growing understanding of the pathogenically relevant molecular signaling pathways opens new possibilities of pharmacological corrections at the second messenger level. Here, the respective know-how of endogenous modulators, such as adenosine, might be used. The aim should be a titration of the glia reaction in order to maintain supposed beneficial functions of reactive microglia and to prevent the dangerous involvement of astrocytes.
Schubert
Peter
P
Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany. Schubert@neuro.mpg.de
Ferroni
Stefano
S