| First Author | Noda S | Year | 2022 |
| Journal | Mol Brain | Volume | 15 |
| Issue | 1 | Pages | 54 |
| PubMed ID | 35701754 | Mgi Jnum | J:327559 |
| Mgi Id | MGI:7287106 | Doi | 10.1186/s13041-022-00936-5 |
| Citation | Noda S, et al. (2022) Impaired mitochondrial accumulation and Lewy pathology in neuron-specific FBXO7-deficient mice. Mol Brain 15(1):54 |
| abstractText | Parkinson's disease, the second most common neurodegenerative disorder, is characterized by the loss of nigrostriatal dopamine neurons. FBXO7 (F-box protein only 7) (PARK15) mutations cause early-onset Parkinson's disease. FBXO7 is a subunit of the SCF (SKP1/cullin-1/F-box protein) E3 ubiquitin ligase complex, but its neuronal relevance and function have not been elucidated. To determine its function in neurons, we generated neuronal cell-specific FBXO7 conditional knockout mice (FBXO7(flox/flox): Nestin-Cre) by crossing previously characterized FBXO7 floxed mice (FBXO7(flox/flox)) with Nestin-Cre mice (Nestin-Cre). The resultant Fbxo7(flox/flox): Nestin-Cre mice showed juvenile motor dysfunction, including hindlimb defects and decreased numbers of dopaminergic neurons. Fragmented mitochondria were observed in dopaminergic and cortical neurons. Furthermore, p62- and synuclein-positive Lewy body-like aggregates were identified in neurons. Our findings highlight the unexpected role of the homeostatic level of p62, which is regulated by a non-autophagic system that includes the ubiquitin-proteasome system, in controlling intracellular inclusion body formation. These data indicate that the pathologic processes associated with the proteolytic and mitochondrial degradation systems play a crucial role in the pathogenesis of PD. |
