Intranasal delivery of BMP2/6 recombinant proteins attenuating Parkinsonian pathology-induced neuronal degeneration

Parkinson’s disease (PD) is characterized by the progressive degeneration of nigrostriatal dopaminergic neurons (DAn), which highlights the importance of neuroprotective strategies that target critical pathways for DAn maintenance. The BMP2/6-SMAD1 signaling axis plays a pivotal role in the development and functional maturation of nigrostriatal dopaminergic neuronal circuits, suggesting the therapeutic potential of BMP2/6 for DAn in PD. In vitro, A53T-α-synuclein-overexpressing neural stem cells obtained by lentiviral transduction were treated with recombinant BMP2/6. In vivo, mice with 6-hydroxydopamine- and α-synuclein preformed fibril lesions received intranasal delivery of mouse BMP2/6 recombinant proteins. Recombinant BMP2/6 treatment improved the viability, proliferation, and differentiation capacity of A53T‑α‑synuclein‑overexpressing neural stem cells, suggesting that BMP2/6 may exert protective effects on the survival and differentiation of DAn. In vivo, intranasal delivery of mouse BMP2/6 recombinant proteins to PD mice significantly delayed DAn neurodegeneration. There was also improved motor function in rotarod tests and apomorphine-induced rotation tests. These findings suggest that BMP2/6 may reduce DAn death in PD models, indicating a potential role for early neuroprotection.