Deciphering variability in the role of interleukin-1β in Parkinson’s disease

Although the role of inflammation in neurodegeneration has been well acknowledged, less is known on the issue of each cytokine in specific neurodegenerative diseases. In this review, we will present evidence elucidating that interleukin-1β (IL-1β) has a multi-faceted character in pathogenesis of Parkinson's disease, which is a progressive neurodegenerative disorder. Increased levels of IL-1β were found in PD patients. Besides, PD symptoms were observed in IL-1β wild-type, but not deficient, animals. These lines of evidence suggest that IL-1β may contribute to the initiation or progression of PD. On the other hand, some studies reported decreased levels of IL-1β in PD patients. Also, genetic studies provided evidence suggesting that IL-1β may protect individuals against PD. Presumably, the broad range of IL-1β role is due to its interaction with both upstream and downstream mediators. Differences in IL-1β levels could be because of glia population (i.e. microglia and astrocytes), mitogen-activated protein kinase and nuclear factor κ light-chain-enhancer of activated B cells signaling pathways, and several mediators (including cyclooxygenase, neurotrophic factors, reactive oxygen species, caspases, heme oxygenase-1, and matrix metalloproteinases). Although far from practice at this point, unraveling theoretical therapeutic targets based on the up-down IL-1β neuroweb could facilitate the development of strategies that are likely to be used for pharmaceutical designs of anti-neurodegenerative drugs of the future.