کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5814270 1556625 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model
چکیده انگلیسی


- We examine the anti-inflammatory effect of geniposide in an AD mouse model.
- Geniposide reduces Aβ accumulation in APP/PS1 mice.
- Geniposide attenuates Aβ-induced synaptic dysfunction.
- Geniposide improves learning and memory deficits in APP/PS1 mice.

The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to Aβ-induced pathogenic responses. Geniposide, a pharmacologically active component purified from gardenia fruit, could attenuate the oligomeric Aβ1-42-induced inflammatory response by blocking the ligation of Aβ to RAGE and suppressing the RAGE-mediated signaling in vitro. Here, we investigated whether geniposide can exert protective effects on the neuroinflammation and memory deficits in an Alzheimer's disease (AD) mouse model. The results indicate that geniposide treatment significantly suppresses RAGE-dependent signaling (activation of ERK and IκB/NF-κB), the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and cerebral Aβ accumulation in vivo. Furthermore, we demonstrate that geniposide augments synaptic plasticity by attenuating the Aβ-induced reduction of long-term potentiation and increasing the miniature excitatory postsynaptic current (mEPSC) amplitude and frequency in hippocampal neurons. In addition, the intragastric administration of geniposide improves learning and memory in APP/PS1 mice. Taken together, these studies indicate that geniposide has profound multifaceted neuroprotective effects in an AD mouse model. Geniposide demonstrates its neuroprotection by inhibiting inflammation, ameliorating amyloid pathology and improving cognition. Thus, geniposide may be a potential therapeutic agent for halting and preventing AD progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 89, February 2015, Pages 175-184
نویسندگان
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