22R‐Hydroxycholesterol protects neuronal cells from β‐amyloid‐induced cytotoxicity by binding to β‐amyloid peptide

doi:10.1046/j.1471-4159.2002.01202.x

Paper

22R‐Hydroxycholesterol protects neuronal cells from β‐amyloid‐induced cytotoxicity by binding to β‐amyloid peptide

Published Dec 1, 2002 · Z. Yao, Rachel C Brown, G. Teper

Journal of Neurochemistry

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45

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Abstract

22R‐hydroxycholesterol, a steroid intermediate in the pathway of pregnenolone formation from cholesterol, was found at lower levels in Alzheimer's disease (AD) hippocampus and frontal cortex tissue specimens compared to age‐matched controls. β‐Amyloid (Aβ) peptide has been shown to be neurotoxic and its presence in brain has been linked to AD pathology. 22R‐hydroxycholesterol was found to protect, in a dose‐dependent manner, against Aβ‐induced rat sympathetic nerve pheochromocytoma (PC12) and differentiated human Ntera2/D1 teratocarcinoma (NT2N) neuron cell death. Other steroids tested were either inactive or acted on rodent neurons only. The effect of 22R‐hydroxycholesterol was found to be stereospecific because its enantiomer 22S‐hydroxycholesterol failed to protect the neurons from Aβ‐induced cell death. Moreover, the effect of 22R‐hydroxycholesterol was specific for Aβ‐induced cell death because it did not protect against glutamate‐induced neurotoxicity. The neuroprotective effect of 22R‐hydroxycholesterol was seen when using Aβ1−42 but not the Aβ25−35 peptide. To investigate the mechanism of action of 22R‐hydroxycholesterol we examined the direct binding of this steroid to Aβ using a novel cholesterol‐protein binding blot assay. Using this method the direct specific binding, under native conditions, of 22R‐hydroxycholesterol to Aβ1−42 and Aβ17−40, but not Aβ25−35, was observed. These data suggest that 22R‐hydroxycholesterol binds to Aβ and the formed 22R‐hydroxycholesterol/Aβ complex is not toxic to rodent and human neurons. We propose that 22R‐hydroxycholesterol offers a new means of neuroprotection against Aβ toxicity by inactivating the peptide.

In Vitro Study

Study Snapshot

22R-hydroxycholesterol offers a new neuroprotective strategy against amyloid toxicity by binding to the peptide and inactivating it.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

22R‐Hydroxycholesterol protects neuronal cells from β‐amyloid‐induced cytotoxicity by binding to β‐amyloid peptide

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