Dataset Information


?-synuclein Induces Mitochondrial Dysfunction through Spectrin and the Actin Cytoskeleton.

ABSTRACT: Genetics and neuropathology strongly link ?-synuclein aggregation and neurotoxicity to the pathogenesis of Parkinson's disease and related ?-synucleinopathies. Here we describe a new Drosophila model of ?-synucleinopathy based on widespread expression of wild-type human ?-synuclein, which shows robust neurodegeneration, early-onset locomotor deficits, and abundant ?-synuclein aggregation. We use results of forward genetic screening and genetic analysis in our new model to demonstrate that ?-synuclein expression promotes reorganization of the actin filament network and consequent mitochondrial dysfunction through altered Drp1 localization. Similar changes are present in a mouse ?-synucleinopathy model and in postmortem brain tissue from patients with ?-synucleinopathy. Importantly, we provide evidence that the interaction of ?-synuclein with spectrin initiates pathological alteration of the actin cytoskeleton and downstream neurotoxicity. These findings suggest new therapeutic approaches for ?-synuclein induced neurodegeneration.


PROVIDER: S-EPMC5755717 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4966315 | BioStudies
1000-01-01 | S-EPMC3799334 | BioStudies
2020-01-01 | S-EPMC7456087 | BioStudies
2014-01-01 | S-EPMC4156029 | BioStudies
1000-01-01 | S-EPMC6085656 | BioStudies
2019-01-01 | S-EPMC7212549 | BioStudies
2019-01-01 | S-EPMC6571045 | BioStudies
1000-01-01 | S-EPMC2769182 | BioStudies
2012-01-01 | S-EPMC3461828 | BioStudies
2020-01-01 | S-EPMC7487555 | BioStudies