Minocycline and ALZ

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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