FIG. 4.

Therapeutic Strategies for PD. Several targeted approaches are currently available or proposed for the treatment of PD. The first of these targets the aggregated or misfolded proteins themselves in an effort to prevent oligomerization induce neuronal damage and microglial activation. Vaccine-induced antibodies or intracellular-produced single chain antibodies directed against misfolded proteins, or drugs (e.g., rapamycin) that stimulate phagocytosis by mononuclear phagocytes, and lysosomal degradation has been proposed for the clearance of extracellular and intracellular aggregated proteins. Alternatively, drugs that affect inflammatory responses, directly inhibit neurotoxicity (by inhibiting apoptotic pathways or excitotoxcity), or promote neuroprotection (e.g., glial derived neurotrophic factor, GDNF) have shown to be effective in animal models for human disease. Finally, efforts are being made to modulate the immune response to aggregated proteins through either immune modifiers or antioxidants that attenuate microglial activation, with the observation that disease can either be exacerbated by effector T cells specific for neo-epitopes or ameliorated by regulatory T cells. Therefore, therapeutic intervention by immunomodulators or adjuvants to induce or upregulate regulatory T cell responses can inhibit ongoing adaptive and innate immune responses and prevent further neurodegeneration.