Pathological glial reactions in neurodegenerative disorders: prospects for future therapeutics

Abstract

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 β-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 respectiveknow-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.

• calcium signaling
• IL-1β-inhibition
• protective adenosine
• reactive astrocytes
• reactive microglia
• receptor cross-talk
• reinforced cAMP signaling
• reinforced cGMP signaling
• TNF-α-inhibition
• upregulated glia reaction