کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8652007 1573344 2018 40 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protection against the Neurotoxic Effects of β-Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of α7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Protection against the Neurotoxic Effects of β-Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of α7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases
چکیده انگلیسی
The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP), expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase (MAPK) in primary cultured neurons and SH-SY5Y cells overexpressing human APP670/671. Lovastatin attenuated the neurotoxic effects of β-amyloid peptide (Aβ) and affected the metabolism of APP, reducing levels of Aβ1 to Aβ42 and β-site amyloid precursor protein-cleaving enzyme 1; enhancing those of αAPP, disintegrin metalloproteinase domain-containing protein 10, and β-site amyloid precursor protein-cleaving enzyme 2; and up-regulating expression of α7 nAChR and stimulating phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Interestingly, methyllycaconitine, an antagonist of α7 nAChR, attenuated this effect on αAPP, but not on phospho-ERK1/2; whereas U0126, an inhibitor of MAPK/ERK kinase/ERK, blocked both the elevated expression of α7 nAChR and enhanced secretion of αAPP. Our findings indicate that lovastatin up-regulates expression of α7 nAChR by a mechanism involving activation of the MAPK/ERK pathway, which may result in diminished production of Aβ.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 188, Issue 4, April 2018, Pages 1081-1093
نویسندگان
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