TRPV4-mediated Ca²⁺ deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons.

ABSTRACT: Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca²⁺ permeable nonselective cation channel, cause TRPV4-related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4-mediated Ca²⁺ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain-of-function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons

SUBMITTER: Sun X 

PROVIDER: S-EPMC10714070 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature