Drug Discov Ther. 2026;20(3):264-268. (DOI: 10.5582/ddt.2026.01017)

Docosahexaenoic acid increases tyrosine hydroxylase phosphorylation at Ser40 without increasing tyrosine hydroxylase protein expression in differentiated NG108-15 cells

Miyazawa D, Katsurayama N, Sato H, Suzuki K, Tahira T, Mizutani H

Tyrosine hydroxylase (TH) is the rate‑limiting enzyme in catecholamine biosynthesis, and its activity is regulated by its phosphorylation at specific serine (Ser) residues. In the present study, we investigated the effects of docosahexaenoic acid (DHA) supplementation on TH protein expression and phosphorylation at Ser31 and Ser40 during differentiation in the neuroblastoma–glioma hybrid cell line NG108-15. TH protein expression and phosphorylation levels were analyzed on day 0 (undifferentiated) and on days 5 and 6 (differentiated). Differentiation increased TH protein expression on days 5 and 6, and DHA supplementation did not affect these increases. Phosphorylation at Ser31 showed no significant change with differentiation. By contrast, phosphorylation at Ser40 exhibited a significant increase with increasing days of differentiation, and this was further augmented by DHA treatment. Collectively, these findings suggest that DHA enhances TH phosphorylation, particularly at Ser40, without affecting TH protein expression. DHA may therefore influence brain function not through changes in TH expression levels, but rather through the phosphorylation of TH at Ser40.

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