Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion
المؤلفون المشاركون
Hortobágyi, Tibor
Šimić, Goran
Babić Leko, Mirjana
Župunski, Vera
Kirincich, Jason
Smilović, Dinko
Hof, P. R.
المصدر
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-18، 18ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-01-15
دولة النشر
مصر
عدد الصفحات
18
التخصصات الرئيسية
الملخص EN
Two clinically distinct diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), have recently been classified as two extremes of the FTD/ALS spectrum.
The neuropathological correlate of FTD is frontotemporal lobar degeneration (FTLD), characterized by tau-, TDP-43-, and FUS-immunoreactive neuronal inclusions.
An earlier discovery that a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 (C9orf72) gene causes ALS and FTD established a special subtype of ALS and FTLD with TDP-43 pathology (C9FTD/ALS).
Normal individuals carry 2–10 hexanucleotide GGGGCC repeats in the C9orf72 gene, while more than a few hundred repeats represent a risk for ALS and FTD.
The proposed molecular mechanisms by which C9orf72 repeat expansions induce neurodegenerative changes are C9orf72 loss-of-function through haploinsufficiency, RNA toxic gain-of-function, and gain-of-function through the accumulation of toxic dipeptide repeat proteins.
However, many more cellular processes are affected by pathological processes in C9FTD/ALS, including nucleocytoplasmic transport, RNA processing, normal function of nucleolus, formation of membraneless organelles, translation, ubiquitin proteasome system, Notch signalling pathway, granule transport, and normal function of TAR DNA-binding protein 43 (TDP-43).
Although the exact molecular mechanisms through which C9orf72 repeat expansions account for neurodegeneration have not been elucidated, some potential therapeutics, such as antisense oligonucleotides targeting hexanucleotide GGGGCC repeats in mRNA, were successful in preclinical trials and are awaiting phase 1 clinical trials.
In this review, we critically discuss each proposed mechanism and provide insight into the most recent studies aiming to elucidate the molecular underpinnings of C9FTD/ALS.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Babić Leko, Mirjana& Župunski, Vera& Kirincich, Jason& Smilović, Dinko& Hortobágyi, Tibor& Hof, P. R.…[et al.]. 2019. Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion. Behavioural Neurology،Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1128952
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Babić Leko, Mirjana…[et al.]. Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion. Behavioural Neurology No. 2019 (2019), pp.1-18.
https://search.emarefa.net/detail/BIM-1128952
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Babić Leko, Mirjana& Župunski, Vera& Kirincich, Jason& Smilović, Dinko& Hortobágyi, Tibor& Hof, P. R.…[et al.]. Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion. Behavioural Neurology. 2019. Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1128952
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1128952
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