EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease

  title={EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease},
  author={Flaubert Tchantchou and Yanan Xu and Yanjue Wu and Yves Christen and Yuan Luo},
  journal={The FASEB Journal},
  pages={2400 - 2408}
Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer's disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Aβ) oligomerization in vitro, protects neuronal cells against Aβ toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1… 

Ginkgo biloba Extract EGb 761 and Its Specific Components Elicit Protective Protein Clearance Through the Autophagy-Lysosomal Pathway in Tau-Transgenic Mice and Cultured Neurons.

It is demonstrated that long-term treatment with Ginkgo biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology through mechanisms against multiple AD pathogenic processes.

Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons.

The present findings suggest that enhanced neurogenesis and synaptogenesis by bilobalide and quercetin may share a common final signaling pathway mediated by phosphorylation of CREB.

Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice.

It is suggested that repeated intake of Gb would enhance cell proliferation and neuroblast differentiation in the mouse DG.

Restoration of impaired phosphorylation of cyclic AMP response element‐binding protein (CREB) by EGb 761 and its constituents in Aβ‐expressing neuroblastoma cells

It is demonstrated that Ginkgo biloba extract, EGb 761, displayed the neuron protective effect by activating the CREB signaling pathway and was blocked by inhibitors of several upstream signaling pathways of CREB, including protein kinase C, ERK, ribosomal S6 kinase(RSK)90 and nitric oxide pathway.

Ginkgo biloba Extract (EGb 761®) Inhibits Glutamate‐induced Up‐regulation of Tissue Plasminogen Activator Through Inhibition of c‐Fos Translocation in Rat Primary Cortical Neurons

It is demonstrated that EGb 761 can modulate tPA activity under basal and glutamate‐stimulated conditions by both translational and transcriptional mechanisms, suggesting it could be a potential and effective therapeutic strategy in tPA‐excessive neurotoxic conditions.



Disruption of neurogenesis by amyloid β‐peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease

The proliferation and survival of NPC in the dentate gyrus of the hippocampus was reduced in mice transgenic for a mutated form of amyloid precursor protein that causes early onset familial AD.

Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease

An age‐dependent decrease in SGZ proliferation in homozygous PDAPP mice is reported, suggesting altered neurogenesis in the PDAPP mouse may contribute to the age‐related cognitive deficits reported in this model of AD and may be a useful adjunct target for assessing the impact of AD therapies.

Amyloid-β-Induced Pathological Behaviors Are Suppressed by Ginkgo biloba Extract EGb 761 and Ginkgolides in Transgenic Caenorhabditis elegans

It is reported that EGb 761 and one of its components, ginkgolide A, alleviates Aβ-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans.

Amyloid β-peptide inhibition of the PKA/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling

It is demonstrated that amyloid β-peptide treatment of cultured hippocampal neurons leads to the inactivation of protein kinase A (PKA) and persistence of its regulatory subunit PKAIIα, suggesting that Αβ acts directly on the pathways involved in the formation of late LTP and agents that enhance the cAMP/PKA/CREB-signaling pathway have potential for the treatment of AD.

Increased hippocampal neurogenesis in Alzheimer's disease

  • K. JinA. Peel D. Greenberg
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
It is suggested that neurogenesis is increased in AD hippocampus, where it may give rise to cells that replace neurons lost in the disease, and that stimulating hippocampal neuroGenesis might provide a new treatment strategy.

Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761

  • Yuan LuoJ. Smith P. Butko
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
It is reported that EGb761 inhibits formation of amyloid-β (Aβ) fibrils, which are the diagnostic, and possibly causative, feature of AD, and suggests that neuronal damage in AD might be due to a direct Aβ toxicity and the apoptosis initiated by the mitochondria.

Regulation of Neurogenesis in Adult Mouse Hippocampus by cAMP and the cAMP Response Element-Binding Protein

The results suggest that the cAMP–CREB cascade could contribute to the actions of neurotransmitters and neurotrophic factors on adult neurogenesis.

Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications.

EGb 761 possesses antioxidant and free radical-scavenging activities, it reverses age-related losses in brain alpha 1-adrenergic, 5-HT1A and muscarinic receptors, protects against ischaemic neuronal death, preserves the function of the hippocampal mossy fiber system, increases hippocampal high-affinity choline uptake, and opposes the detrimental effects of ischaemia.