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Review
. 2018 Mar 23:10:75.
doi: 10.3389/fnagi.2018.00075. eCollection 2018.

U1 snRNP Alteration and Neuronal Cell Cycle Reentry in Alzheimer Disease

Bing Bai  1
Affiliations
Review

U1 snRNP Alteration and Neuronal Cell Cycle Reentry in Alzheimer Disease

Bing Bai. Front Aging Neurosci. .

Abstract

The aberrancy of U1 small nuclear ribonucleoprotein (snRNP) complex and RNA splicing has been demonstrated in Alzheimer's disease (AD). Importantly, the U1 proteopathy is AD-specific, widespread and early-occurring, thus providing a very unique clue to the AD pathogenesis. The prominent feature of U1 histopathology is its nuclear depletion and redistribution in the neuronal cytoplasm. According to the preliminary data, the initial U1 cytoplasmic distribution pattern is similar to the subcellular translocation of the spliceosome in cells undergoing mitosis. This implies that the U1 mislocalization might reflect the neuronal cell cycle-reentry (CCR) which has been extensively evidenced in AD brains. The CCR phenomenon explains the major molecular and cellular events in AD brains, such as Tau and amyloid precursor protein (APP) phosphorylation, and the possible neuronal death through mitotic catastrophe (MC). Furthermore, the CCR might be mechanistically linked to inflammation, a critical factor in the AD etiology according to the genetic evidence. Therefore, the discovery of U1 aberrancy might strengthen the involvement of CCR in the AD neuronal degeneration.

Keywords: Alzheimer’s disease; U1 snRNP; cell cycle reentry; cytoplasmic redistribution; inflammation.

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Figures

Figure 1
Figure 1
The summarized model of Alzheimer’s disease (AD) pathogenesis. The amyloid precursor protein (APP) derived Aβ species initiates the inflammation with the exacerbation by other insults to drive the neuronal cell cycle events.
See this image and copyright information in PMC

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