Journal
REVISTA MEXICANA DE NEUROCIENCIA
Volume 22, Issue 3, Pages 124-131Publisher
ACAD MEXICANA NEUROLOGIA
DOI: 10.24875/RMN.20000108
Keywords
Alzheimer's disease; Tau protein; Amyloid Beta; Chromatin; Lamin A; Neuronal nucleus
Categories
Funding
- Fundacion Alfonso X el Sabio-Banco Santander, Spain [1.010.924]
Ask authors/readers for more resources
Dementia, with Alzheimer's disease as its most common cause, has seen a significant increase in recent years. The nuclear origin of AD suggests that neuronal DNA repair mechanisms may lead to the accumulation of Tau protein in the cytoplasm, resulting in dementia.
Dementia is a public health problem with an extraordinary increase in recent years. Alzheimer's disease (AD) is the most common cause of dementia. This disease has been considered a consequence of cytoplasmic and extracellular accumulations of Tau protein and amyloid, respectively. Nevertheless, a nuclear origin of AD has recently emerged. Both Tau protein and the nuclear lamin protect the nuclear and chromatin organization for proper gene expression throughout neuronal life. Accumulation of DNA damage, mainly as a result of aging, drives post-mitotic neurons to initiate DNA repair by entering the cell cycle. The complexity of the nucleus-cytoskeleton prevents neurons from dividing and condemns them to a state of hyperdiploidy ending in neuronal death, after transiently prolonging their life. In AD, hippocampal neurons survive their fatal fate by triggering an aberrant structural and functional transformation of the nucleus. Lamin A expression and Tau protein transfer to the cytoplasm results in loss of the protector role of nuclear Tau and the subsequent global chromatin disorganization. Therefore, the cytoplasmic Tau protein accumulations that characterize AD are consequence of the attempted neuronal repair. Alzheimer's neurons with unstructured nuclei and aberrant cytoskeletons manage to survive by sacrificing their plasticity, which inexorably leads to dementia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available