Schematic hypothesis of glial activations in the S tg mouse. Astrocytes may quickly respond to S released from degenerating neurons to protect against neurodegeneration. During the long time course of neurodegeneration, these activated astrocytes may lose their protective properties or might be aberrantly activated, leading to stimulation of neuroinflammation. This process may be stimulated by loss of function of DJ-1. In contrast, microglia may be protective during the early stage of neurodegeneration and are not readily activated unless they are stimulated with LPS or with alterations of other familial PD risk factors such as Parkin, PINK1, LRRK2, and other members of the synuclein family of peptides, including mutant S.