scholarly journals Regulator of Cell Cycle (RGCC) Expression during the Progression of Alzheimer's Disease

2017 ◽  
Vol 26 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Scott E. Counts ◽  
Elliott J. Mufson
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neuronal Cell ◽  
Cyclin B1 ◽  
Multifunctional Protein ◽  
Protein Levels ◽  
Cell Cycle Reentry ◽  
M Phase

Unscheduled cell cycle reentry of postmitotic neurons has been described in cases of mild cognitive impairment (MCI) and Alzheimer's disease (AD) and may form a basis for selective neuronal vulnerability during disease progression. In this regard, the multifunctional protein regulator of cell cycle (RGCC) has been implicated in driving G1/S and G2/M phase transitions through its interactions with cdc/cyclin-dependent kinase 1 (cdk1) and is induced by p53, which mediates apoptosis in neurons. We tested whether RGCC levels were dysregulated in frontal cortex samples obtained postmortem from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), MCI, or AD. RGCC mRNA and protein levels were upregulated by ~50%-60% in MCI and AD compared to NCI, and RGCC protein levels were associated with poorer antemortem global cognitive performance in the subjects examined. To test whether RGCC might regulate neuronal cell cycle reentry and apoptosis, we differentiated neuronotypic PC12 cultures with nerve growth factor (NGF) followed by NGF withdrawal to induce abortive cell cycle activation and cell death. Experimental reduction of RGCC levels increased cell survival and reduced levels of the cdk1 target cyclin B1. RGCC may be a candidate cell cycle target for neuroprotection during the onset of AD.

scholarly journals mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease

2016 ◽  
Vol 13 (2) ◽  
pp. 152-167 ◽  
Author(s):  
Andrés Norambuena ◽  
Horst Wallrabe ◽  
Lloyd McMahon ◽  
Antonia Silva ◽  
Eric Swanson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Neuronal Cell ◽  
Cell Cycle Reentry ◽  
Brain Insulin

scholarly journals Microglial derived tumor necrosis factor-α drives Alzheimer's disease-related neuronal cell cycle events

2014 ◽  
Vol 62 ◽  
pp. 273-285 ◽  
Author(s):  
Kiran Bhaskar ◽  
Nicole Maphis ◽  
Guixiang Xu ◽  
Nicholas H. Varvel ◽  
Olga N. Kokiko-Cochran ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Neuronal Cell ◽  
Factor Α ◽  
Necrosis Factor

DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients and a Transgenic Model of the Disease

2021 ◽  
pp. 1-16
Author(s):  
Esteban Leyton ◽  
Diego Matus ◽  
Sandra Espinoza ◽  
José Matías Benitez ◽  
Bastián I. Cortes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Real Time ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Protein Levels ◽  
5Xfad Mice

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

S5-01-01: The pathway from amyloid to tau for aberrant neuronal cell cycle re-entry in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_20) ◽  
pp. P724-P724
Author(s):  
Matthew Seward ◽  
Eric Swanson ◽  
Erik Roberson ◽  
George Bloom
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Neuronal Cell

scholarly journals Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer’s Disease Progression

2020 ◽  
Vol 21 (5) ◽  
pp. 1841
Author(s):  
Laura Gil ◽  
Sandra A. Niño ◽  
Erika Chi-Ahumada ◽  
Ildelfonso Rodríguez-Leyva ◽  
Carmen Guerrero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Lamin A ◽  
Neuronal Populations ◽  
Cell Cycle Reentry ◽  
Epigenetic Marker ◽  
Age Related ◽  
Elevated Expression

Background. Recent reports point to a nuclear origin of Alzheimer’s disease (AD). Aged postmitotic neurons try to repair their damaged DNA by entering the cell cycle. This aberrant cell cycle re-entry involves chromatin modifications where nuclear Tau and the nuclear lamin are involved. The purpose of this work was to elucidate their participation in the nuclear pathological transformation of neurons at early AD. Methodology. The study was performed in hippocampal paraffin embedded sections of adult, senile, and AD brains at I-VI Braak stages. We analyzed phospho-Tau, lamins A, B1, B2, and C, nucleophosmin (B23) and the epigenetic marker H4K20me3 by immunohistochemistry. Results. Two neuronal populations were found across AD stages, one is characterized by a significant increase of Lamin A expression, reinforced perinuclear Lamin B2, elevated expression of H4K20me3 and nuclear Tau loss, while neurons with nucleoplasmic Lamin B2 constitute a second population. Conclusions. The abnormal cell cycle reentry in early AD implies a fundamental neuronal transformation. This implies the reorganization of the nucleo-cytoskeleton through the expression of the highly regulated Lamin A, heterochromatin repression and building of toxic neuronal tangles. This work demonstrates that nuclear Tau and lamin modifications in hippocampal neurons are crucial events in age-related neurodegeneration.

scholarly journals Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease

2019 ◽  
Vol 11 (474) ◽  
pp. eaau6550 ◽  
Author(s):  
Brendan P. Lucey ◽  
Austin McCullough ◽  
Eric C. Landsness ◽  
Cristina D. Toedebusch ◽  
Jennifer S. McLeland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Eye Movement ◽  
Single Channel ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Rapid Eye Movement ◽  
Tau Pathology ◽  
Potential Marker

In Alzheimer’s disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical tau pathology is frequently already present. The period in which AD pathology is accumulating in the absence of cognitive symptoms represents a clinically relevant time window for therapeutic intervention. Sleep is increasingly recognized as a potential marker for AD pathology and future risk of cognitive impairment. Previous studies in animal models and humans have associated decreased non–rapid eye movement (NREM) sleep slow wave activity (SWA) with Aβ deposition. In this study, we analyzed cognitive performance, brain imaging, and cerebrospinal fluid (CSF) AD biomarkers in participants enrolled in longitudinal studies of aging. In addition, we monitored their sleep using a single-channel electroencephalography (EEG) device worn on the forehead. After adjusting for multiple covariates such as age and sex, we found that NREM SWA showed an inverse relationship with AD pathology, particularly tauopathy, and that this association was most evident at the lowest frequencies of NREM SWA. Given that our study participants were predominantly cognitively normal, this suggested that changes in NREM SWA, especially at 1 to 2 Hz, might be able to discriminate tau pathology and cognitive impairment either before or at the earliest stages of symptomatic AD.

scholarly journals Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats

2004 ◽  
Vol 279 (21) ◽  
pp. 22684-22692 ◽  
Author(s):  
Yi Wen ◽  
Shaohua Yang ◽  
Ran Liu ◽  
Anne Marie Brun-Zinkernagel ◽  
Peter Koulen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Cerebral Ischemia ◽  
Neuronal Cell ◽  
Transient Cerebral Ischemia ◽  
Female Rats
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