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Abstract
This article is a comprehensive assessment of the quantitative features of the dose response for neuroprotective agents and their underlying mechanistic foundations. The data were derived from published studies using numerous primary neuronal cell cultures and neuronal cell lines. These biological models assessed normal developmental and aging processes, preconditioning adaptive responses, and various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The nature of the dose response was generally U-shaped with quantitative features similar to the hormetic dose-response model and independent of biological model, endpoint measured, and chemical class. The agents displaying the U-shaped dose response for neuronal survival include numerous endogenous agonists, plant-derived agents, synthetic drugs, and widely used chemicals including potent neurotoxins. That neuroprotective agents display similar dose-response relationships regardless of experimental system, potency, and endpoint is an important observation with widespread biomedical and clinical implications.