Proteomics of human iPSC derived dopaminergic neurons with a Parkinson's disease linked PARK7/DJ-1 mutation

ABSTRACT: Parkinson’s disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered iPSC midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein accumulation. In-depth proteomics, state-of-the-art imaging, and ultrasensitive DA probes uncovered that decreased VMAT2 protein and function impaired vesicular DA uptake, resulting in reduced vesicle availability and abnormal vesicle morphology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Dopaminergic Neuron

DISEASE(S): Parkinson's Disease

SUBMITTER: Stephan Mueller  

LAB HEAD: Stefan F. Lichtenthaler

PROVIDER: PXD069663 | Pride | 2026-01-07

REPOSITORIES: Pride