Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity

Abstract

A variety of ‘-omic’ technologies are being increasingly applied in preclinical safety assessments. Such approaches, however, have not been implemented in neurotoxicity safety evaluations. Current regulatory guidelines for assessing neurotoxicity emphasise reliance on traditional histopathological stains and behavioural testing batteries. Although these methods may be sufficient to detect some neurotoxic effects, they lack both the sensitivity and specificity required for broad-scale neurotoxicity screening. The glial reaction to nervous system damage, often termed gliosis, represents a hallmark of all types of nervous system injury. As such, the development and implementation of gliosis biomarkers represents a broadly applicable approach for neurotoxicity safety assessment. Using a panel of known neurotoxic agents, the authors have shown that the astroglial protein, glial fibrillary acidic protein (GFAP), can serve as one such biomarker of neurotoxicity. Qualitative and quantitative analysis of GFAP has shown this biomarker to be a sensitive and specific indicator of the neurotoxic condition. The implementation of GFAP and related glial biomarkers in neurotoxicity screens may serve as the basis for further development of molecular signatures predictive of adverse effects on the nervous system

Keywords::

• biomarkers
• drug development
• drug safety assessment
• drug toxicolgy
• glial biomarkers
• glial fibrillary acidic protein (GFAP)
• gliosis
• molecular neurotoxicology
• preclinical drug screening