ACS Chemical Neuroscience
Research Article
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were completed by X.Y.; AFM studies were performed by T.S.
and D.Y.; PAMPA-BBB studies were completed by M.E. and
M.I.R.-F.; LC-MS/MS studies were completed by K.L. and
M.S.H.; BBB studies in mice were performed by S.T.;
Experiment design, data analysis, writing, and editing were
completed by S.Z.
Funding
The PAMPA-BBB studies were partially supported by the
Spanish Ministry of Economy and Competitiveness (SAF2012-
31035). The work was supported in part by the Alzheimer’s &
Related Diseases Research Award Fund, Commonwealth of
Virginia (S.Z.) and the NIA of the NIH under Award Number
R01AG041161 (S.Z.), and the American Heart Association
13POST16360022 (S.T.).
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We thank Dr. George M. Martin at the University of
Washington, Seattle for kindly providing the MC65 cells. We
are grateful to Dr. Dave R. Schubert at the Salk Institute, La
Jolla, California for providing the HT22 cells. We also thank
Dr. Antonio Abbate, Department of Internal Medicine, VCU,
for the BBB studies in the mice.
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interventions are needed for Alzheimer’s disease. Mol. Neurobiol. 41,
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ABBREVIATIONS
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Recept. 9, 203−212.
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M., and Tolosa de Talamoni, N. (2012) New perspectives in
melatonin uses. Pharmacol. Res. 65, 437−444.
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Swaab, D. F. (2003) Early neuropathological Alzheimer’s changes in
aged individuals are accompanied by decreased cerebrospinal fluid
melatonin levels. J. Pineal Res. 35, 125−130.
(18) Hatfield, C. F., Herbert, J., van Someren, E. J., Hodges, J. R., and
Hastings, M. H. (2004) Disrupted daily activity/rest cycles in relation
to daily cortisol rhythms of home-dwelling patients with early
Alzheimer’s dementia. Brain 127, 1061−1074.
(19) Rosales-Corral, S., Acuna-Castroviejo, D., Tan, D. X., Lopez-
Armas, G., Cruz-Ramos, J., Munoz, R., Melnikov, V. G., Manchester, L.
C., and Reiter, R. J. (2012) Accumulation of exogenous amyloid-beta
peptide in hippocampal mitochondria causes their dysfunction: a
protective role for melatonin. Oxid. Med. Cell. Longevity 2012, 843649.
(20) Pandi-Perumal, S. R., BaHammam, A. S., Brown, G. M., Spence,
D. W., Bharti, V. K., Kaur, C., Hardeland, R., and Cardinali, D. P.
(2013) Melatonin antioxidative defense: therapeutical implications for
aging and neurodegenerative processes. Neurotoxic. Res. 23, 267−300.
(21) Hardeland, R. (2012) Melatonin in aging and disease -multiple
consequences of reduced secretion, options and limits of treatment.
Aging Dis. 3, 194−225.
(22) Esatbeyoglu, T., Huebbe, P., Ernst, I. M., Chin, D., Wagner, A.
E., and Rimbach, G. (2012) Curcumin–from molecule to biological
function. Angew. Chem., Int. Ed. 51, 5308−5332.
(23) Wong, Y.-S., Peuchmaur, M. A., Marechal, E., Botte, C., Vial, H.
J., and Saidani, N. (2009) Preparation of novel polyspirane compounds
■
Aβ, amyloid-β; AβOs, amyloid-β oligomers; AD, Alzheimer’s
disease; AFM, atomic force microscopy; BBB, blood-brain
barrier; CNS, central nervous system; DCFH-DA, dichloro-
fluorescein diacetate; DMPU, N,N′-dimethylpropyleneurea;
DMEM, Dulbecco’s modified Eagle’s medium; DMSO,
dimethyl sulfoxide; ESI, electrospray ionization; FBS, fetal
bovine serum; HPLC, high performance liquid chromatog-
raphy; LC, liquid chromatography; mitoROS, mitochondrial
reactive oxygen species; mPTP, mitochondrial permeability
transition pore; MS, mass spectrometry; MTT, 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NAC,
N-acetylcysteine; PAMPA, parallel artificial membrane perme-
ability; PBS, phosphate buffered saline; PMA, phosphomolyb-
dic acid; ROS, reactive oxygen species; SAR, structure−activity
relationship; SDS-PAGE, sodium dodecyl sulfate-polyacryla-
mide gel electrophoresis; SEM, standard error of mean; SRM,
selected reaction monitoring; TBS, Tris buffered saline; TC,
tetracycline; TFA, trifluoroacetic acid; THF, tetrahydrofuran;
ThT, thioflavin T; TLC, thin-layer chromatography; TMS,
tetramethylsilane
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dx.doi.org/10.1021/cn500081s | ACS Chem. Neurosci. XXXX, XXX, XXX−XXX