Cellular fibronectin exacerbates α-synuclein aggregation via integrin alpha4beta1 mediated PARP1 and SCD elevation.

ABSTRACT: Mitochondrial dysfunction and lipid metabolic disturbance may promote pathologic α-synuclein (α-syn) aggregation, accelerating the progression of Parkinson's disease (PD). Whether extracellular matrices are associated with those pathological mechanisms in PD remains elusive. Here, we aimed to identify if cellular fibronectin (cFn), a component of extracellular matrices, contributes to α-syn abnormality via inducing mitochondrial energy depletion or disrupting lipid homeostasis. In Our study, 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-treated PD mice and human neuronal SH-SY5Y cells were used. Astrocyte-derived cFn protein delivery and AAV-mediated cFn knockdown mouse models were established to validate the functional role of cFn. Mitochondrial dysfunction was detected by transmis

SUBMITTER: Huang Z 

PROVIDER: S-EPMC12664477 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature