| First Author | Dutta D | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 2 | Pages | 111058 |
| PubMed ID | 35830804 | Mgi Jnum | J:339111 |
| Mgi Id | MGI:7316245 | Doi | 10.1016/j.celrep.2022.111058 |
| Citation | Dutta D, et al. (2022) Treadmill exercise reduces alpha-synuclein spreading via PPARalpha. Cell Rep 40(2):111058 |
| abstractText | This study underlines the importance of treadmill exercise in reducing alpha-synuclein (alpha-syn) spreading in the A53T brain and protecting nigral dopaminergic neurons. Preformed alpha-syn fibril (PFF) seeding in the internal capsule of young A53T alpha-syn mice leads to increased spreading of alpha-syn to substantia nigra and motor cortex and concomitant loss of nigral dopaminergic neurons. However, regular treadmill exercise decreases alpha-syn spreading in the brain and protects nigral dopaminergic neurons in PFF-seeded mice. Accordingly, treadmill exercise also mitigates alpha-synucleinopathy in aged A53T mice. While investigating this mechanism, we have observed that treadmill exercise induces the activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in the brain to stimulate lysosomal biogenesis via TFEB. Accordingly, treadmill exercise remains unable to stimulate TFEB and reduce alpha-synucleinopathy in A53T mice lacking PPARalpha, and fenofibrate, a prototype PPARalpha agonist, reduces alpha-synucleinopathy. These results delineate a beneficial function of treadmill exercise in reducing alpha-syn spreading in the brain via PPARalpha. |
