Cell Press Reviews>Trends in Neurosciences, 2019>1-13
We hypothesize that Parkinson’s disease (PD) pathogenesis can be divided intothree temporal phases. During the first phase, ‘triggers’, such as viral infectionsor environmental toxins, spark the disease process in the brain and/or periph-eral tissues. Triggers alone, however, may be insufficient, requiring ‘facilitators’like peripheral inflammation for PD pathology to develop. Once the diseasemanifests, ‘aggravators’ spur further neurodegeneration and exacerbate symp-toms. Aggravators are proposed to include impaired autophagy and cell-to-cellpropagation of a-synuclein pathology. We believe clinical trials need to con-sider these three phases and target potential therapies at the appropriate stageof the disease process in order to be effective.
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