S RAMBOZ1 WASHINGTON A1, RAYNEL S1, JASON B1, NICOLE C1, SHEILYN N1, KIMBERLY C1, KIM C1, KENDALL W1.
1PsychoGenics, Tarrytown, NY, USA
Aggregation of mis-folded proteins is a feature common to many neurodegenerative diseases. In Parkinson’s disease, characterized neuropathologically by the presence of intraneuronal Lewy bodies and Lewy neuritis, the attention has been particularly focused on mis-folded and aggregated α synuclein (fibrillar α synuclein) which is a major component of both Lewy bodies and Lewy neurites. Experimental studies and a growing body of evidence has emerged demonstrating that synthetic α synuclein fibrils (both human and murine) are capable of ‘seeding’ and propagating α synuclein pathology not only in α synuclein transgenic mouse models but importantly in non-transgenic (WT) neuronal cultures and mice (Luk, K.C. et al., 2012a ; Luk, K.C. et al., 2012b; Volpicelli-Daley, L.A. et al., 2014). PsychoGenics has extensive experience working with both human and murine synthetic alpha synuclein fibrils in a variety of murine neurodegenerative disease models. Stereotaxic administration of 5μg of murine pre-formed fibrils (Proteos Inc.) is sufficient to induce a progressive α synuclein pathology, reduced dopamine levels and motor deficits in murine models (Martinez, T. et al., SFN 2014). As a continuation of our previous study sponsored by the Michael J Fox Foundation, PsychoGenics has expanded the study in WT mice as well as other murine models to assess the behavioral and pathological consequences of α synuclein propagation and aggregation.