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.

P3-319: Elevated expression of cell cycle proteins in very early stages of Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T615-T615
Author(s):  
Juan C. Troncoso ◽  
Miguel A. Riudavets ◽  
Marcelo Schultz ◽  
Gustavo Sevlever ◽  
Gay Rudow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Cell Cycle Proteins ◽  
Early Stages ◽  
Elevated Expression

scholarly journals Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1308
Author(s):  
Shang-Der Chen ◽  
Jenq-Lin Yang ◽  
Yi-Heng Hsieh ◽  
Tsu-Kung Lin ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Memory Loss ◽  
Oxygen Species ◽  
Mechanistic Target Of Rapamycin ◽  
Cell Cycle Reentry ◽  
Age Related ◽  
Reduce Activity

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

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

Alzheimer’s disease: as it was in the beginning

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Stanislav Kozlov ◽  
Alexei Afonin ◽  
Igor Evsyukov ◽  
Andrei Bondarenko
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Metal Ion ◽  
Aberrant Cell ◽  
Molecular Abnormalities ◽  
Model Of Alzheimer’S Disease ◽  
Age Related

AbstractSince Alzheimer’s disease was first described in 1907, many attempts have been made to reveal its main cause. Nowadays, two forms of the disease are known, and while the hereditary form of the disease is clearly caused by mutations in one of several genes, the etiology of the sporadic form remains a mystery. Both forms share similar sets of neuropathological and molecular manifestations, including extracellular deposition of amyloid-beta, intracellular accumulation of hyperphosphorylated tau protein, disturbances in both the structure and functions of mitochondria, oxidative stress, metal ion metabolism disorders, impairment of N-methyl-D-aspartate receptor-related signaling pathways, abnormalities of lipid metabolism, and aberrant cell cycle reentry in some neurons. Such a diversity of symptoms led to proposition of various hypotheses for explaining the development of Alzheimer’s disease, the amyloid hypothesis, which postulates the key role of amyloid-beta in Alzheimer’s disease development, being the most prominent. However, this hypothesis does not fully explain all of the molecular abnormalities and is therefore heavily criticized. In this review, we propose a hypothetical model of Alzheimer’s disease progression, assuming a key role of age-related mitochondrial dysfunction, as was postulated in the mitochondrial cascade hypothesis. Our model explains the connections between all the symptoms of Alzheimer’s disease, with particular attention to autophagy, metal metabolism disorders, and aberrant cell cycle re-entry in neurons. Progression of the Alzheimer’s disease appears to be a complex process involving aging and too many protective mechanisms affecting one another, thereby leading to even greater deleterious effects.

Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease

2004 ◽  
Vol 75 (5) ◽  
pp. 698-703 ◽  
Author(s):  
Xiongwei Zhu ◽  
Andrew McShea ◽  
Peggy L.R. Harris ◽  
Arun K. Raina ◽  
Rudy J. Castellani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Cyclin B ◽  
M Phase ◽  
Elevated Expression

scholarly journals CDT2-controlled cell cycle reentry regulates the pathogenesis of Alzheimer's disease

2018 ◽  
Vol 15 (2) ◽  
pp. 217-231 ◽  
Author(s):  
Fang Huang ◽  
Minghui Wang ◽  
Rong Liu ◽  
Jian-Zhi Wang ◽  
Eric Schadt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Cell Cycle Reentry

scholarly journals Emerging Roles of Inhibitor of Differentiation-1 in Alzheimer’s Disease: Cell Cycle Reentry and Beyond

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1746
Author(s):  
Shang-Der Chen ◽  
Jenq-Lin Yang ◽  
Yi-Chun Lin ◽  
A-Ching Chao ◽  
Ding-I Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Mammalian Cells ◽  
Senile Plaques ◽  
Adult Population ◽  
Cell Cycle Reentry ◽  
Id Proteins ◽  
Underlying Mechanisms

Inhibitor of DNA-binding/differentiation (Id) proteins, a family of helix-loop-helix (HLH) proteins that includes four members of Id1 to Id4 in mammalian cells, are critical for regulating cell growth, differentiation, senescence, cell cycle progression, and increasing angiogenesis and vasculogenesis, as well as accelerating the ability of cell migration. Alzheimer’s disease (AD), the most common neurodegenerative disease in the adult population, manifests the signs of cognitive decline, behavioral changes, and functional impairment. The underlying mechanisms for AD are not well-clarified yet, but the aggregation of amyloid-beta peptides (Aβs), the major components in the senile plaques observed in AD brains, contributes significantly to the disease progression. Emerging evidence reveals that aberrant cell cycle reentry may play a central role in Aβ-induced neuronal demise. Recently, we have shown that several signaling mediators, including Id1, hypoxia-inducible factor-1 (HIF-1), cyclin-dependent kinases-5 (CDK5), and sonic hedgehog (Shh), may contribute to Aβ-induced cell cycle reentry in postmitotic neurons; furthermore, Id1 and CDK5/p25 mutually antagonize the expression/activity of each other. Therefore, Id proteins may potentially have clinical applications in AD. In this review article, we introduce the underlying mechanisms for cell cycle dysregulation in AD and present some examples, including our own studies, to show different aspects of Id1 in terms of cell cycle reentry and other signaling that may be crucial to alter the neuronal fates in this devastating neurodegenerative disease. A thorough understanding of the underlying mechanisms may provide a rationale to make an earlier intervention before the occurrence of cell cycle reentry and subsequent apoptosis in the fully differentiated neurons during the progression of AD or other neurodegenerative diseases.

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