Minocycline Attenuates Neuronal Cell Death & Improves Cognitive Impairment in Alzheimer's Disease

1: Neuropsychopharmacology. 2007 Apr 4;

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive
Impairment in Alzheimer's Disease Models.


Choi Y, Kim HS, Shin KY, Kim EM, Kim M, Kim HS, Park CH, Jeong YH, Yoo
J, Lee JP, Chang KA, Kim S, Suh YH.
1Department of Pharmacology, College of Medicine, National Creative
Research Initiative Center for Alzheimer's Dementia and Neuroscience
Research Institute, MRC, Seoul National University, Seoul, South
Korea.

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 alpha and
caspase 12 activation induced by amyloid beta peptide(1-42) treatment
in NGF-differentiated PC 12 cells.


In addition, increases in the phosphorylation of eukaryotic
translation initiation factor-2 alpha were attenuated by
administration of minocycline in Tg2576 mice, which harbor mutated
human APP695 gene including the Swedish double mutation and amyloid
beta peptide(1-42)-infused rats.


We found that minocycline administration attenuated deficits in
learning and memory in amyloid beta peptide(1-42)-infused rats.

Increased phosphorylated state of eukaryotic translation initiation
factor-2 alpha 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.

PMID: 17406652

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