ArticleFrontiers in aging neuroscience2026
Evaluation of peripheral and intranigral AAV-mediated Irisin delivery in a chronic AAV-A53T α-Synuclein overexpression mouse model of Parkinson's disease.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra and pathological aggregation of α-Synuclein (α-Syn). Although Irisin has shown neuroprotective effects in acute MPTP-induced and α-Syn preformed fibrils (PFFs) propagation models, its therapeutic effects in a chronic α-Syn overexpression model remain incompletely defined. Methods: In the present study, we evaluated the effects of AAV8-Irisin delivered either peripherally via tail vein injection or centrally via direct intranigral co-administration in the AAV9-A53T mouse model. Results: Under the tested doses, routes, and intervention schedule, neither peripheral nor intranigral AAV8-Irisin delivery produced statistically significant improvements in behavioral performance, dopaminergic neuron survival, α-Synuclein pathology, glial activation, or AQP4 polarization; however, numerical trends were observed in select measures, including motor coordination and TH-positive neuron counts. Conclusion: These findings suggest that, under the current experimental conditions, a clear neuroprotective benefit of Irisin was not readily detectable in this model. Whether modest effects might emerge under different exposure levels, intervention windows, or adequately powered designs remains unknown.
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