Metabolic manifestations of Parkinson’s disease in cell models derived from induced pluripotent stem cells

Induced pluripotent stem cell (iPSC)-based models represent an innovative approach to studying the pathogenesis of inherited Parkinson’s disease (PD) at molecular and cellular levels. The ability to derive neurons, astrocytes, and microglia carrying SNCA gene mutations from iPSCs significantly advances our understanding of key metabolic disturbances in PD. Each specific type of SNCA gene mutation (A53T, A30P, triplications, duplications, etc.) exhibits individual effects on functional and biochemical characteristics of differentiated cells. These differences involve synaptogenesis, extramitochondrial oxygen consumption, and protein metabolism. The diversity of effects makes critical the selection of strictly defined iPSC lines depending on research objectives. The aim of this review is to examine metabolic features of brain cells derived from iPSCs with inherited PD associated with SNCA mutations, as well as the potential of using iPSCs to develop personalized in vitro models for understanding disease mechanisms. This approach will facilitate identification of new therapeutic targets and refinement of existing technologies for diagnosis and targeted therapy.