Long-term exposure to PFE-360 in the AAV-α-synuclein rat model: findings and implications

Abstract

Significance statementTreatment of Parkinsons disease is reliant on symptomatic treatments, without any option to slow or halt disease progression. Mutations in LRRK2 and -synuclein are known risk factors for Parkinsons disease. Presence of -synuclein aggregates at autopsies in both idiopathic and most G2019S cases is suggestive of a common disease pathogenesis. LRRK2 and -synuclein interaction is hypothesized to play a pivotal role in the pathological mechanisms and inhibitors of LRRK2 are investigated as novel disease modulatory treatments in the clinic. However, preclinical in vivo evidence of a beneficial effect of LRRK2 inhibition is mixed and limited. This study increases our understanding of LRRK2 as a mediator of neuronal dysfunction and the potential of LRRK2 as a promising target in PD.