Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking of curable treatments to date. Adeno-associated virus (AAV) vectors make gene therapy an effective strategy in treating neurological disorders. Despite… Click to show full abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking of curable treatments to date. Adeno-associated virus (AAV) vectors make gene therapy an effective strategy in treating neurological disorders. Despite Kaspar and colleagues have showed that AAV-IGF1 delivery successfully prolonged the survival of SOD1G93A mice, whether IGF-1 act as a protective role in the TDP-43 mutant model still have not been reported. In this study, we proved that AAV9 vector mediated expression of human wild-type IGF-1 protected TDP-25 cells from apoptosis and oxidative stress. Furthermore, we demonstrated that the hIGF-1 exerted its neuroprotective effect through an Akt-dependent manner in cultured motoneurons. We also described a hypothesis that in cultured TDP-25-associated degeneration of motoneurons, the neuronal survival promotion of IGF-1 was related to VEGF.
               
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