GENERATION OF PATIENT-SPECIFIC NEURONS PROVIDES AN IN VITRO MODEL OF PARKINSON'S DISEASE TO IDENTIFY EARLY MOLECULAR FEATURES OF NEURODEGENERATION

Abstract

PARKINSON?S DISEASE (PD), ONE OF THE MOST COMMON HUMAN NEURODEGENERATIVE DISORDERS IN CENTRAL NERVOUS SYSTEM, HAS BEEN ACTIVELY STUDIED OVER THE LAST DECADE. SEVERAL GENE VARIANTS, INCLUDING PARK2, LRRK2, AND SNCA, HAVE BEEN IDENTIFIED AND IMPLICATED IN THE DEGENERATION OF MIDBRAIN DOPAMINERGIC (MDA) NEURONS. HOWEVER, THE MOLECULAR DETAILS OF THE PROGRESSION OF PD ASSOCIATED WITH DISTINCT GENETIC VARIATIONS HAVE NOT BEEN SUFFICIENTLY CLARIFIED. RECENT STUDIES OF HUMAN DISEASES, SUCH AS PD, HAVE TAKEN ADVANTAGE OF PATIENT-DERIVED INDUCED PLURIPOTENT STEM CELLS (IPSCS) TO RECAPITULATE ASPECTS OF THE DISEASE IN VITRO. THESE APPROACHES TO DISEASE MODELING CAN PROVIDE INSIGHTS TO THE DISEASE PROCESS AND REVEAL MOLECULAR CHANGES ASSOCIATED WITH DISEASE PROGRESSION. IN THIS STUDY, MULTIPLE PD IPS CELL LINES CARRYING DISTINCT GENETIC VARIANTS WERE EMPLOYED TO IDENTIFY COMMON MOLECULAR DYSREGULATION UNDERLYING PD PROGRESSION. BY USING OPTIMIZED DIFFERENTIATION PROTOCOLS, PATIENT-SPECIFIC MDA N