Induced Pluripotent Stem Cell Lines as a Model for Studying the Cellular Phase of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a complex neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) as a result of intraneural deposition of aggregated alpha-synuclein (aSyn) in Lewy bodies (LB). aSyn is an intrinsically-disordered protein, encoded by the SNCA gene, and is implicated in both familial and sporadic forms of PD. However, we still do not fully understand if and how aSyn causes cell dysfunction and death. Therefore, it is essential to develop and explore robust models for bridging the gap between preclinical research and clinical applications, creating platforms for testing hypotheses and assessing potential interventions. The emergence of patient-derived induced pluripotent stem cells (iPSCs) offers unique opportunities for investigating the cellular phase of PD and related synucleinopathies by enabling the systematic assessment of phenotypes in various cell types of relevance for disease. Moreover, advances in PD-derived iPSC technology also hold promise for cell replacement therapy and drug discovery efforts using pharmacological or genetic screening approaches. In this review, we focus on the application of aSyn iPSC models in PD research, summarizing their anticipated merits, challenges and present-day implementations.