Figure 1.

Time-course of the mechanisms leading to selective neuronal degeneration.

Microglial and astrocytic activation occurs early in the neurodegenerative process and produces maladaptive changes of many components of the pentapartite synapse (including extracellular matrix and blood brain barrier). The release of inflammatory and toxic factors by glial cells impairs mitochondrial energy production and is associated with the release of ROS. These slowly progressive mechanisms finally initiate neuronal degeneration, however the disease onset occurs later, after failure of rescue mechanisms and progression of neuronal degeneration. BBB: Blood-brain barrier; ECM: extracellular matrix; M1, M2, A1, A2: microglial and astrocytic type 1 and type 2 phenotypes; ROS: reactive oxygen species.