Abstract
Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood–brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases. In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models. Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNA-dependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 α and caspase 12 activation induced by amyloid β peptide1–42 treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 α were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid β peptide1–42-infused rats. We found that minocycline administration attenuated deficits in learning and memory in amyloid β peptide1–42-infused rats. Increased phosphorylated state of eukaryotic translation initiation factor-2 α is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity. On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.
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Acknowledgements
This work was supported by a National Creative Research Initiative Grant (2006–2009) from MOST, in part by the BK21 Human Life Sciences program and by a grant from Seoul National University Bundang Hospital Research Fund.
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Choi, Y., Kim, HS., Shin, K. et al. Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models. Neuropsychopharmacol 32, 2393–2404 (2007). https://doi.org/10.1038/sj.npp.1301377
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DOI: https://doi.org/10.1038/sj.npp.1301377
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