Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model.
There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12-13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment.
Department of Surgery, Physicians & Surgeons College of Columbia University, New York, NY 10032, USA.
Fang
F
Fang
Xiaochun
X
Chen
Tianwen
T
Huang
Lih-Fen
LF
Lue
John S
JS
Luddy
Shirley Shidu
SS
Yan
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects
C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D053829:Amyloid Precursor Protein Secretases; C035054:ginsenoside Rg1