Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer’s disease (AD).
Researchers found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice.
Amyloid-β oligomers reduced BRCA1 levels in primary neuronal cultures. In wild-type mice, knocking down neuronal BRCA1 in the dentate gyrus caused increased DNA double-strand breaks, neuronal shrinkage, synaptic plasticity impairments, and learning and memory deficits, but not apoptosis.
Low levels of hAPP/Amyloid-β overexpression exacerbated these effects. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic N-methyl-D-aspartate receptors promoted the proteasomal degradation of BRCA1.
Authors conclude that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.
http://www.nature.com/ncomms/2015/151130/ncomms9897/full/ncomms9897.html
Edited
Latest News
Functional heterogeneity of…
By newseditor
Posted 13 May
Gut bacteria produced compo…
By newseditor
Posted 13 May
Role of ECM in brain memory
By newseditor
Posted 13 May
All individuals with two co…
By newseditor
Posted 12 May
Autoantibody patterns in pa…
By newseditor
Posted 12 May
Other Top Stories
Skin keratinocytes are involved the warm temperature sensation
Read more
How insulin-like growth factors facilitate brain plasticity
Read more
How sensory neurons impact the gut
Read more
How cellular powerhouses call for help when under stress
Read more
Intermittent fasting improves Alzheimer's pathology
Read more
Protocols
Mime-seq 2.0: a method to s…
By newseditor
Posted 13 May
Improved detection of DNA r…
By newseditor
Posted 09 May
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
Publications
Pharmacological induction o…
By newseditor
Posted 13 May
The Effect of Glycine and N…
By newseditor
Posted 13 May
Diindoles produced from com…
By newseditor
Posted 13 May
Endothelial cell expression…
By newseditor
Posted 13 May
Senescence: A DNA damage re…
By newseditor
Posted 13 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar