Aberrancies in signal transduction and cell cycle related events in Alzheimer’s disease

1998 ◽  
pp. 147-158 ◽  
Author(s):  
T. Arendt ◽  
M. Holzer ◽  
U. Gärtner ◽  
M. K. Brückner
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Signal Transduction

Untangling the role of tau in Alzheimer’s disease: A unifying hypothesis

2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Neha Bhatia ◽  
Garth Hall
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Tau Protein ◽  
Membrane Trafficking ◽  
The Past ◽  
The Brain ◽  
Associated Abnormalities

AbstractRecent investigations into the etiology and pathogenesis of Alzheimer’s disease (AD) in the past few years have expanded to include previously unexplored and/or disconnected aspects of AD and related conditions at both the cellular and systemic levels of organization. These include how AD-associated abnormalities affect the cell cycle and neuronal differentiation state and how they recruit signal transduction, membrane trafficking and protein transcytosis mechanisms to produce a neurotoxic syndrome capable of spreading itself throughout the brain. The recent expansion of AD research into intercellular and new aspects of cellular degenerative mechanisms is causing a systemic re-evaluation of AD pathogenesis, including the roles played by well-studied elements, such as the generation of Aβ and tau protein aggregates. It is also changing our view of neurodegenerative diseases as a whole. Here we propose a conceptual framework to account for some of the emerging aspects of the role of tau in AD pathogenesis.

The Phosphoinositide Signal Transduction Pathway in the Pathogenesis of Alzheimer’s Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Vincenza Rita Lo Vasco
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Membrane Trafficking ◽  
Hormone Secretion ◽  
Signal Transduction Pathway ◽  
Brain Morphology ◽  
Signal Transduction Pathways ◽  
Transduction Pathway ◽  
Cell Functions

Background: During aging and in age-associated disorders, such as Alzheimer's Disease (AD), learning abilities decline. Probably, disturbances in signal transduction in brain cells underlie the cognitive decline. The phosphorylation/dephosphorylation imbalance occurring in degenerating neurons was recently related to abnormal activity of one or more signal transduction pathways. AD is known to be associated with altered neuronal Ca<sup>2+</sup> homeostasis, as Ca<sup>2+</sup> accumulates in affected neurons leading to functional impairment. It is becoming more and more evident the involvement of signal transduction pathways acting upon Ca<sup>2+</sup> metabolism and phosphorylation regulation of proteins. A growing interest raised around the role of signal transduction systems in a number of human diseases including neurodegenerative diseases, with special regard to the systems related to the phosphoinositide (PI) pathway and AD. The PI signal transduction pathway plays a crucial role, being involved in a variety of cell functions, such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, cell and tissue polarity, and contributes to regulate the Ca<sup>2+</sup> levels in the nervous tissue. Conclusion: A number of observations indicated that PI-specific phospholipase C (PLC) enzymes might be involved in the alteration of neurotransmission. To understand the role and the timing of action of the signalling pathways recruited during the brain morphology changes during the AD progression might help to elucidate the aetiopathogenesis of the disease, paving the way to prognosis refinement and/or novel molecular therapeutic strategies.

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

scholarly journals Pathogenic tau disrupts the cellular program that maintains neuronal identity

2021 ◽  
Author(s):  
Adrian Beckmann ◽  
Paulino Ramirez ◽  
Maria Gamez ◽  
William J. Ray ◽  
Bess Frost
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Therapeutic Approaches ◽  
Nuclear Pleomorphism ◽  
Mesenchymal Transition ◽  
Neuronal Identity ◽  
Cell Cycle Activation

AbstractNeurons in human Alzheimer’s disease acquire phenotypes that are also present in various cancers, including over-stabilization of the cytoskeleton, nuclear pleomorphism, decondensation of constitutive heterochromatin, and aberrant activation of the cell cycle. Unlike in cancer, in which cell cycle activation drives tumor formation, activation of the cell cycle in post-mitotic neurons is sufficient to induce neuronal death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer’s disease and related “tauopathies.” We have combined network analysis of human Alzheimer’s disease and mouse tauopathy with mechanistic studies in Drosophila to discover that pathogenic forms of tau drive abortive cell cycle activation by disrupting the cellular program that maintains neuronal identity. Mechanistically, we identify Moesin, a prognostic biomarker for cancer and mediator of the epithelial-mesenchymal transition (EMT), as a major effector of tau-induced neurotoxicity. We find that aberrant activation of Moesin in neurons acts through the actin cytoskeleton to dysregulate the cellular program that maintains neuronal identity. Our study identifies mechanistic parallels between tauopathy and cancer and sets the stage for novel therapeutic approaches.

Disturbances in signal transduction mechanisms in Alzheimer's disease

1995 ◽  
Vol 149-150 (1) ◽  
pp. 287-292 ◽  
Author(s):  
Christopher J. Fowler ◽  
Richard F. Cowburn ◽  
Anita Garlind ◽  
Bengt Winblad ◽  
Cora O'Neill
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Transduction Mechanisms

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

Signal Transduction in Alzheimer’s Disease

Neurosignals ◽  
2002 ◽  
Vol 11 (5) ◽  
pp. 235-235 ◽  
Author(s):  
Mark A. Smith ◽  
Xiongwei Zhu ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction

Putative Factors Interfering Cell Cycle Re-Entry in Alzheimer’s Disease: An Omics Study with Differential Expression Meta-Analytics and Co-Expression Profiling

2021 ◽  
pp. 1-26
Author(s):  
Sze Chung Yuen ◽  
Simon Ming-Yuen Lee ◽  
Siu-wai Leung
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Expression Analysis ◽  
Protein Interaction ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Tau Proteins ◽  
Related Factors ◽  
Protein Protein Interaction

Background: Neuronal cell cycle re-entry (CCR) is a mechanism, along with amyloid-β (Aβ) oligomers and hyperphosphorylated tau proteins, contributing to toxicity in Alzheimer’s disease (AD). Objective: This study aimed to examine the putative factors in CCR based on evidence corroboration by combining meta-analysis and co-expression analysis of omic data. Methods: The differentially expressed genes (DEGs) and CCR-related modules were obtained through the differential analysis and co-expression of transcriptomic data, respectively. Differentially expressed microRNAs (DEmiRNAs) were extracted from the differential miRNA expression studies. The dysregulations of DEGs and DEmiRNAs as binary outcomes were independently analyzed by meta-analysis based on a random-effects model. The CCR-related modules were mapped to human protein-protein interaction databases to construct a network. The importance score of each node within the network was determined by the PageRank algorithm, and nodes that fit the pre-defined criteria were treated as putative CCR-related factors. Results: The meta-analysis identified 18,261 DEGs and 36 DEmiRNAs, including genes in the ubiquitination proteasome system, mitochondrial homeostasis, and CCR, and miRNAs associated with AD pathologies. The co-expression analysis identified 156 CCR-related modules to construct a protein-protein interaction network. Five genes, UBC, ESR1, EGFR, CUL3, and KRAS, were selected as putative CCR-related factors. Their functions suggested that the combined effects of cellular dyshomeostasis and receptors mediating Aβ toxicity from impaired ubiquitination proteasome system are involved in CCR. Conclusion: This study identified five genes as putative factors and revealed the significance of cellular dyshomeostasis in the CCR of AD.

Sign in / Sign up

Export Citation Format

Share Document