B Ghirotto et al
Non-motor Parkinson disease (PD) symptoms, including gastrointestinal (GI) symptoms such as chronic constipation and abdominal bloating, commonly predate motor symptoms in PD patients. The current study investigates the possibility that the enteric nervous system (ENS), which is involved in intestinal immunity, plays a role in these early PD GI symptoms. The authors cite previous work implicating α-synuclein (α-syn), whose protein misfolding and aggregation defines PD pathology and used iPSC derived enteric neural lineage (ENL) cells to study PD pathology. PD patient LCLs with a genetic triplication in the α-syn gene were used to reprogram the iPSCs that were then differentiated into ENLs. These iPSC-ENLs were then used as an in vitro model system to study the impact of increased α-syn. The authors found that increased α-syn results in a metabolic vulnerability in iPSC-ENLs that negatively impacted several downstream biological processes via TNF, including mitochondrial function and oxidative stress. More generally, this study describes a new in vitro model system for early stage PD that can be used for future studies into PD progression and treatment.
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