Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease.
Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.
Matsubara
Etsuro
E
Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Bryant-Thomas
Tara
T
Pacheco Quinto
Javier
J
Henry
Tracey L
TL
Poeggeler
Burkhard
B
Herbert
Donald
D
Cruz-Sanchez
Felix
F
Chyan
Yau-Jan
YJ
Smith
Mark A
MA
Perry
George
G
Shoji
Mikio
M
Abe
Koji
K
Leone
Anna
A
Grundke-Ikbal
Inge
I
Wilson
Glen L
GL
Ghiso
Jorge
J
Williams
Christina
C
Refolo
Lorenzo M
LM
Pappolla
Miguel A
MA
Chain
Daniel G
DG
Neria
Eyal
E
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D015996:Survival Rate
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009566:Nitrates; D011506:Proteins; D008550:Melatonin