Select Page

K. R. WALKER, W. ARIAS, J. BERGER, N. CHIRICHELLA, B. S. NUNEZ, R. SPRINGER, K. CIRILLO, J. SANCHEZ-PADILA, G. TOMBAUGH, A. GHAVAMI, S. RAMBOZ

Psychogenics Inc., Tarrytown, NY

Aggregation of mis-folded proteins is a feature common to many neurodegenerative diseases. Parkinson’s disease is a progressive movement disorder which is characterized neuropathologically by the presence of intraneuronal Lewy bodies and Lewy neurites. Alpha synuclein is a highly soluble pre-synaptic protein that is implicated in vesicular trafficking. Mis-folded and aggregated α synuclein (fibrillar α synuclein) is a major component of both Lewy bodies and Lewy neurites. Experimental studies have demonstrated that cerebral injection of brain lysates from α synuclein aggegrate bearing transgenic mice into pre-symptomatic young transgenic mice accelerates formation of α synuclein pathology (Luk, K.C. et al., 2012). 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.