Studies on the effects of peripheral inflammation on the progression of Parkinson ´s disease

Inflammation is the first line of defense of the organism after an insult is detected. Although usually beneficial, it could be detrimental if its magnitude or duration is not adequate. In the brain, both, neurodegenerative and neuroprotective roles for inflammation, and especially for microglia activation, have been postulated during the course of neurodegenerative diseases such Alzheimer's (AD) and prion disease. Recently, it has been shown that an inflammatory reaction with similar characteristics as in AD and prion disease, is present during the course of Parkinson's Disease (PD). On the other hand, the current evidence suggests that peripheral inflammation could exacerbate on-going microglial activation. Particulary, there is evidence that systemic infections exacerbate disease progression in Multiple sclerosis, AD and prion disease models. We hypothesize that central or peripheral inflammatory stimuli reaching the brain could influence brain inflammation in PD and shift microglial function towards neurodegeneration, leading to an exacerbation of PD symptoms and disease progression. To prove our working hypothesis we should demonstrate that: A. Exacerbation of inflammation in PD brains leads to increased neurodegeneration or behavioral symptoms of PD. B. Peripheral inflammation can efficiently exacerbate central inflammation and increased neurodegeneration or behavioral symptoms of PD as observed in prion and AD models. C. Inhibition of the exacerbation of central inflammation leads to an amelioration of disease progression. If our working hypothesis proves to be correct, future clinical trials will test whether peripheral inflammatory events could be regarded as risk factors for the progression of PD.