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

摘要: Parkinson9s disease (PD) is a progressive neurodegenerative disorder associated with impaired motor function and several non-motor symptoms, no available modifying treatment. Intracellular accumulation of pathological α-synuclein inclusions hallmark idiopathic PD, whereas, dominant mutations in Leucine-rich repeat kinase 2 (LRRK2) are familial PD that clinically indistinguishable from PD. Recent evidence supports the hypothesis an increase LRRK2 activity development not only but also Previous reports have shown preclinical effects modulation on α-synuclein-induced neuropathology. Increased subthalamic nucleus (STN) burst firing neurotoxin models patients hypothesized to be causally involved deficit To study potential pathophysiological relationship between pathology we investigated effect chronic inhibition AAV-α-synuclein overexpression rat model. In this study, report using PFE-360 partially restores function. However, independent aberrant STN processes. Nonetheless, our finding recapitulates beneficial for treatment possibly driven by mechanisms bypassing importance activity.