Homeostatic Plasticity and Therapeutic Approaches in Neurodegeneration

The synapses transmit signals between neurons in an ever-changing fashion. Changes of synaptic transmission arise from numerous mechanisms known as synaptic plasticity. The importance and complexity of the synapse has fueled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. Particularly, homeostatic plasticity refers to the local changes in synaptic activation to generate local synaptic adaptations and network-wide changes in activity to generate adjustments between excitation and inhibition. This review chapter will focus on synaptic phenomena and mechanisms that are likely to contribute to network homeostasis. In addition, it will be discussed a putative modulation of the signaling mechanisms serving a homeostatic function as a viable therapeutic approach for disease modification in neurological and neurodegenerative disorders. To sum up, the main role of the following players in homeostatic plasticity will be analyzed, based on what a growing body of evidence has suggested recently: BDNF-mediated TrkB system activation; adenosine modulation system; nitric oxide/soluble GC/cGMP signaling; astrocyte involvement astroglial CB1 receptors; the microtubule-associated neuronal protein Tau; the signaling of the Wnt protein family; extracellular vesicles in the intercellular communication; and estrogen involvement in non-reproductive functions.