| First Author | Matsuo K | Year | 2021 |
| Journal | Brain Res | Volume | 1760 |
| Pages | 147383 | PubMed ID | 33636166 |
| Mgi Jnum | J:306946 | Mgi Id | MGI:6706953 |
| Doi | 10.1016/j.brainres.2021.147383 | Citation | Matsuo K, et al. (2021) Suppression of alpha-synuclein propagation after intrastriatal injection in FABP3 null mice. Brain Res 1760:147383 |
| abstractText | Accumulation and aggregation of alpha-synuclein (alphaSyn) trigger neuronal loss in the substantia nigra pars compacta (SNpc), which in turn causes motor symptoms in Parkinson's disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3), an intracellular fatty acid carrier protein, enhances alphaSyn neurotoxicity in SNpc and motor impairments after intranigral injection of alphaSyn fibrils. However, the temporal profile of alphaSyn fibril spread and their toxicity remains unclear. In the present study, we investigated the temporal profile of alphaSyn fibril spread and its toxicity, which induces intracellular fibril formation. Monomeric and fibrillar aSyn assemblies were labeled with ATTO550 to distinguish the exogenous form from the endogenous species and injected into bilateral striatum in Fabp3(+/+) (wild type) and Fabp3(-/-) mice. Accumulation of both monomeric and fibrillar exogenous alphaSyn in the SNpc was drastically decreased in Fabp3(-/-) mice compared to that in the Fabp3(+/+) counterparts. Deletion of Fabp3 also prevented exogenous alphaSyn fibril-induced seeding of the endogenous alphaSyn into aggregates containing phosphorylated and filamentous forms in the SNpc. Consistent with these results, loss of dopaminergic neurons and subsequent impaired motor behavior were attenuated in Fabp3(-/-) mice. These results highlight the crucial role of FABP3 in pathogenic alphaSyn accumulation and its seeding ability. Taken together, FABP3 could be a potential therapeutic target against alphaSyn propagation in synucleinopathies. |
