A recently published long-term retrospective cohort study suggests that the use of thiazolidinediones may reduce the risk of Parkinson’s disease in populations with diabetes. In comparison to metformin use, thiazolidinediones demonstrated a 28% reduced risk of incident Parkinson’s disease.

Pioglitazone and rosiglitazone are examples of thiazolidinediones currently available in Australia. These agents are agonists of peroxisome proliferator-activated receptor gamma (PPARγ). Activation of this receptor is beneficial in diabetes as it modulates the transcription of a number of genes involved in lipid and glucose metabolism.

Loss of dopaminergic neurons in the substantia nigra plays a significant role in the pathogenesis of Parkinson’s disease, and mounting evidence suggests that mitochondrial dysfunction may contribute to this neurodegeneration. Activation of PPARγ increases mitochondrial biogenesis which may partly compensate for the pathology involved in Parkinson’s disease and lead to a reduction in neuroinflammation and dopaminergic neuronal loss. However, it is thought that these neuroprotective effects may only be beneficial if therapy is initiated during the preclinical stages of the disease before advanced neurodegeneration occurs. This may explain the conflicting findings of previous studies with shorter durations.

Further investigation is required to confirm and understand the effect of thiazolidinediones on the incidence of Parkinson’s disease. The PPARγ receptor subfamily is currently the subject of significant interest and research. Other potential applications of therapies targeting PPARγ include obesity, cancer, and inflammatory bowel disease, in addition to their accepted use in diabetes.

References:

  1. Brakedal B, Flønes I, Reiter SF, Torkildsen O, Dölle C, Assmus J, et al. Glitazone use associated with reduced risk of Parkinson’s disease. Mov Disord. 2017; 32(11): 1594-9.
  2. Moon HE, Paek SH. Mitochondrial Dysfunction in Parkinson’s Disease. Exp Neurobiol. 2015; 24(2): 103-16.
  3. Pinto M, Nissanka N, Peralta S, Brambilla R, Diaz F, Moraes CT. Pioglitazone ameliorates the phenotype of a novel Parkinson’s disease mouse model by reducing neuroinflammation. Mol Neurodegener. 2016; 11: 25.

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