Expression of the Newly Identified Gene CAC1 in the Hippocampus of Alzheimer’s Disease Patients

Abstract

Alzheimer's disease (AD), the most common form of senile dementia, is associated with neurodegeneration. The development of Alzheimer's disease is related to abnormalities of cell cycle regulation. Preliminary work showed that a novel gene, CAC1, was highly expressed in tumors and had an oncogene-like function related to cell cycle regulation. The pathogenesis of AD is still incompletely understood. In this study, we measured the expression level of CAC1 in the hippocampus of AD patients to explore the involvement of CAC1 in the development of AD. Our findings showed that the expression level of CAC1 in the hippocampus of AD patients was significantly lower than that of normal controls. The reduction of CAC1 expression did not affect tau/p-tau-396, amyloid precursor protein or apolipoprotein E4 in the in vitro model. A reduction of cyclin E was detected after a CAC1-knockdown. Interestingly, we found that the knockdown of CAC1 by RNAi led to an increase in oxidative stress and the level of p53 protein in SHSY-5Y cells. The expression of CAC1 in SHSY-5Y cells protected the cells from apoptosis induced by Aβ toxicity or oxidative stress. These results established that CAC1 is an important factor for the protection of cells against Aβ toxicity and oxidative stress.

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

“…CACULI, also named CAC1, interacts with the CDK2 protein and governs the activity of CDK2, further regulating the cell cycle. The imbalanced expression of CACULI may lead to cell cycle disorder (Kong et al ). Previous studies have shown that abnormal cell cycle regulation promotes the development of Alzheimer's disease and leads to apoptosis by regulating p53 protein activation.…”

“…Previous studies have shown that abnormal cell cycle regulation promotes the development of Alzheimer's disease and leads to apoptosis by regulating p53 protein activation. Moreover, downregulation of CACUL1 levels activates the p53 signaling pathway (Kong et al ; Fukuda et al ). The activation of the p53 protein, which is an important regulator of apoptosis, has been shown to be involved in promoting the expression of pro‐apoptotic members of the BCL‐2 family (Fukuda et al ; Sharma et al ).…”

Effects of Chronic Scopolamine Treatment on Cognitive Impairments and Myelin Basic Protein Expression in the Mouse Hippocampus

“…The hippocampus, which is an important component of the limbic system, plays a vital role in cognitive processes such as learning, memory consolidation, and information retrieval (Hami et al 2014;Huang et al 2015;Kong et al 2012;Zhao et al 2014). Hippocampal-dependent cognitive function is well known to be influenced largely by the hippocampal cholinergic system (Gold 2003;Hasselmo 2006).…”

CACUL1/CAC1 Regulates the Antioxidant Response by Stabilizing Nrf2

“…It has also been reported that CACUL1 is involved in ERα and RARα regulation by binding to and repressing their transcription activity in cells 36 37 . Moreover CACUL1 has been reported to be down regulated in hippocampus of Alzheimer disease patients, and up-regulated by H 2 O 2 and Aβ in SHSY-5Y cells 38 . It was also shown that CACUL1 knock-down leads to increase in oxidative stress, suggesting a role in cellular stress responses 38 .…”

“…Moreover CACUL1 has been reported to be down regulated in hippocampus of Alzheimer disease patients, and up-regulated by H 2 O 2 and Aβ in SHSY-5Y cells 38 . It was also shown that CACUL1 knock-down leads to increase in oxidative stress, suggesting a role in cellular stress responses 38 . However, its biochemical function and biological relevance in stress response mechanisms is not fully understood.…”