Fecha de publicación: 12/01/2023 Fuente: Wipo Milk or dairy products The two nucleoredoxin genes, NXNL1 and NXNL2 encode by alternative splicing for a secreted truncated thioredoxin that mediates neuronal survival and a thioredoxin enzyme that regulates the phosphorylation of TAU. Behavioral analyses of young Nxnl2-/- mice demonstrate that this gene is involved in regulating of brain functions and is essential for learning and memory exerting positive effects on long-term potentiation (LTP) in the hippocampus. LTP dysfunction on the young Nxnl2-/- mice can be fully corrected by the synergistic action of the two products of the Nxnl2 gene. Aging Nxnl2-/- mice have brain stigmata of tauopathy as seen by oligomerization, phosphorylation and aggregation of TAU. This late occurring tauopathy can be prevented, by recombinant AAVs encoding RdCVF2 and RdCVF2L when administrated to young animals, which is of significant interest for therapeutic perspectives. Therefore, the present invention relates to a method of treating a tauopathy in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a first polynucleotide encoding for the short isoform of the NXNL2 gene, Rod-derived Cone Viability Factor (RdCVF2) and of a second polynucleotide encoding the long isoform of the NXNL2 gene, RdCVF2L.