کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5549062 | 1556600 | 2017 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization
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کلمات کلیدی
DRGTRPV1NGFFluo-3 AMCGRPPreprotachykinin APPTAtrkAB2RBradykinin 2 receptorbradykinin - برادیکینینvanilloid receptor subtype 1 - زیر تیپ گیرنده وانیلیوئید 1nerve growth factor - فاکتور رشد عصبSubstance P - ماده Pdorsal root ganglion neurons - نورونهای گانگلیونی ریشه پشتیcalcitonin gene-related peptide - پپتید مرتبط با ژن کلسی تونینBradykinin receptors - گیرنده های برادیکینین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization](/preview/png/5549062.png)
چکیده انگلیسی
Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a “painless” derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators. NGF61/100 displays a neurotrophic activity on DRG neurons comparable to that of control NGF61, despite a reduced activation of PLCγ, Akt and Erk1/2. NGF61/100 does not differ from NGF61 in its ability to up-regulate Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) expression. However, upon Bradykinin (BK) stimulation, NGF61/100-treated DRG neurons release a much lower amount of SP and CGRP, compared to control NGF61 pre-treated neurons. This effect of painless NGF is explained by the reduced up-regulation of BK receptor 2 (B2R), respect to control NGF61. As a consequence, BK treatment reduced phosphorylation of the transient receptor channel subfamily V member 1 (TRPV1) in NGF61/100-treated cultures and induced a significantly lower intracellular Ca2+ mobilization, responsible for the lower release of noxious mediators. Transcriptomic analysis of DRG neurons treated with NGF61/100 or control NGF allowed identifying a small number of nociceptive-related genes that constitute an “NGF pain fingerprint”, whose differential regulation by NGF61/100 provides a strong mechanistic basis for its selective reduced pain sensitizing actions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 117, 1 May 2017, Pages 134-148
Journal: Neuropharmacology - Volume 117, 1 May 2017, Pages 134-148
نویسندگان
C. Severini, P. Petrocchi Passeri, M.T. Ciotti, F. Florenzano, C. Petrella, F. Malerba, B. Bruni, M. D'Onofrio, I. Arisi, R. Brandi, R. Possenti, P. Calissano, A. Cattaneo,