Researchers have identified what they describe as a threshold dose for chronic D-serine administration in rats, after eight weeks of daily dosing in a Parkinson’s disease model produced signs of kidney injury.
D-serine is an endogenous co-agonist at the glycine binding site of NMDA receptor GluN1 subunits. It is increasingly studied in Parkinson’s disease, where altered levels have been detected in both patients and animal models.
Despite this growing interest, the acute nephrotoxicity of D-serine in rats is well known, and data on chronic exposure have been lacking. The new study, based on a rat model using α-synuclein overexpression, set out to address that gap by evaluating renal effects after eight weeks of daily D-serine administration, given alone or in combination with L-DOPA.
The results showed that a dose of 200 mg/kg induced biological alterations reflected in growth patterns and water consumption, as well as peritubular inflammatory infiltrates in the kidney.
According to the authors, these changes were comparable to the nephrotoxic effect reported after acute treatment, suggesting that 200 mg/kg could represent a threshold dose for chronic D-serine administration in rats.
The findings are intended to provide a useful reference for future studies involving prolonged treatment, helping researchers select doses that avoid renal toxicity when investigating D-serine in Parkinson’s disease models.
Because the work was conducted in rats with α-synuclein overexpression rather than in humans, the results speak to preclinical dosing practice and cannot be directly extrapolated to patients. The study is an original research article published open access in the journal Amino Acids, and the version shared is subject to further editorial edits before the final Version of Record.
Subject of Research: Chronic D-serine nephrotoxicity in a Parkinson's disease rat model
Article Title: Renal effects of chronic D-serine administration in a Parkinson’s disease rat model: evidence for a threshold nephrotoxic dose
Article References: Ferniani, G., Lucotti, C., Fanni, S., Bratzu, J., Lucà , S., Franco, R., Usiello, A., Carta, M., & Borriello, M. (2026). Renal effects of chronic D-serine administration in a Parkinson’s disease rat model: evidence for a threshold nephrotoxic dose. Amino Acids. https://doi.org/10.1007/s00726-026-03571-9
Image Credits: AI Generated
DOI: 10.1007/s00726-026-03571-9
Keywords: D-serine, nephrotoxicity, kidney, Parkinson's disease, rat model, alpha-synuclein, L-DOPA, NMDA receptor, chronic dosing, Amino Acids, Renal, effects
News Source: Diana Fleming. (October 29, 2026). Chronic D-serine at 200 mg/kg shows kidney toxicity signs in Parkinson’s disease rats. Scienmag.
