PPAR agonists as therapeutics for CNS trauma and neurological diseases

Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many preclinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated.

• 1
  PPAR activation inhibits the expression of M1 genes in cells exposed to M1-type stimuli and enhances the expression of M2 markers in the presence of M2 stimuli.
• 2
  PPAR activation suppresses synthesis of inflammatory cytokines/chemokines and reactive oxygen (ROS) and nitrogen (RNS) species, all of which are toxic to oligodendrocytes
• 3
  Activation of PPARs can reduce inflammation and confer neuroprotection, in part through their ability to minimize cell death and reduce mitochondrial dysfunction.