Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|CYP2E1 activation and formation of protein adducts leading to neurodegeneration||AdverseOutcome|
|AChE Inhibition Leading to Neurodegeneration||AdverseOutcome|
Key Event Description
Neurodegeneration is the loss of neuron cells in the brain and spinal cord. The loss of neurons can either be functional loss, also called ataxia, or sensory dysfunction, known as dementia. The brain is organized in different parts which all have their own function in an individual. So which affect the neurodegeneration has on an individual it depends on where neuron loss occurs.
How It Is Measured or Detected
A biomarker is needed since a common way to detect neurodegeneration is with the use of a PET scan. Although this technique works, another in vitro method needed to predict whether a chemical can induce neurodegeneration before it damages a whole brain. A possible biomarker of neurodegeneration can be found in the cerebrospinal fluid. These biomarkers are the spectrin breakdown products, specifically SBDP-145. There are two possible ways of measuring SBDP-145. First quantification can be done with an ELISA technique, from a sample taken out of the cerebrospinal fluid. Another way is to label SBDP-145 with the use of immunohistochemistry, so that the expression and release of SBDP-145 can be made visible.
Domain of Applicability
Regulatory Significance of the Adverse Outcome
Uttara, B., Singh, A. V, Zamboni, P. & Mahajan, R. T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol. 7, 65–74 (2009).
Pritt, M. L. et al. Initial biological qualification of SBDP-145 as a biomarker of compound-induced neurodegeneration in the rat. Toxicol. Sci. 141, 398–408 (2014).