Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis
المؤلفون المشاركون
Patel, Nikunj S.
Sahagan, Barbara G.
Faghihi, Mohammad Ali
Lopez-Toledano, Miguel A.
Wahlestedt, Claes
Modarresi, Farzaneh
المصدر
International Journal of Alzheimer's Disease
العدد
المجلد 2011، العدد 2011 (31 ديسمبر/كانون الأول 2011)، ص ص. 1-11، 11ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2011-07-09
دولة النشر
مصر
عدد الصفحات
11
التخصصات الرئيسية
الملخص EN
Background.
Alzheimer's disease (AD) is a devastating neurological disorder and the main cause of dementia in the elderly population worldwide.
Adult neurogenesis appears to be upregulated very early in AD pathogenesis in response to some specific aggregates of beta-amyloid (Aβ) peptides, exhausting the neuronal stem cell pools in the brain.
Previously, we characterized a conserved nonprotein-coding antisense transcript for β-secretase-1 (BACE1), a critical enzyme in AD pathophysiology.
We showed that the BACE1-antisense transcript (BACE1-AS) is markedly upregulated in brain samples from AD patients and promotes the stability of the (sense) BACE1 transcript.
In the current paper, we examine the relationship between BACE1, BACE1-AS, adult neurogenesis markers, and amyloid plaque formation in amyloid precursor protein (APP) transgenic mice (Tg-19959) of various ages.
Results.
Consistent with previous publications in other APP overexpressing mouse models, we found adult neurogenesis markers to be noticeably upregulated in Tg-19959 mice very early in the development of the disease.
Knockdown of either one of BACE1 or BACE1-AS transcripts by continuous infusion of locked nucleic acid- (LNA-) modified siRNAs into the third ventricle over the period of two weeks caused concordant downregulation of both transcripts in Tg-19959 mice.
Downregulation of BACE1 mRNA was followed by reduction of BACE1 protein and insoluble Aβ.
Modulation of BACE1 and BACE1-AS transcripts also altered oligomeric Aβ aggregation pattern, which was in turn associated with an increase in neurogenesis markers at the RNA and protein level.
Conclusion.
We found alterations in the RNA and protein concentrations of several adult neurogenesis markers, as well as non-protein-coding BACE1-AS transcripts, in parallel with the course of β-amyloid synthesis and aggregation in the brain of Tg15999 mice.
In addition, by knocking down BACE1 or BACE1-AS (thereby reducing Aβ production and plaque deposition), we were able to modulate expression of these neurogenesis markers.
Our findings suggest a distortion of adult neurogenesis that is associated with Aβ production very early in amyloid pathogenesis.
We believe that these alterations, at the molecular level, could prove useful as novel therapeutic targets and/or as early biomarkers of AD.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Modarresi, Farzaneh& Faghihi, Mohammad Ali& Patel, Nikunj S.& Sahagan, Barbara G.& Wahlestedt, Claes& Lopez-Toledano, Miguel A.. 2011. Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis. International Journal of Alzheimer's Disease،Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-508947
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Modarresi, Farzaneh…[et al.]. Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis. International Journal of Alzheimer's Disease No. 2011 (2011), pp.1-11.
https://search.emarefa.net/detail/BIM-508947
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Modarresi, Farzaneh& Faghihi, Mohammad Ali& Patel, Nikunj S.& Sahagan, Barbara G.& Wahlestedt, Claes& Lopez-Toledano, Miguel A.. Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis. International Journal of Alzheimer's Disease. 2011. Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-508947
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-508947
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر