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.

Construction of protocell-based artificial signal transduction pathway

2021 ◽  
Author(s):  
CHONG CHEN ◽  
Xuejing Wang ◽  
Ying Wang ◽  
Liangfei Tian ◽  
Jinxuan Cao
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Signal Transduction Pathways ◽  
Biological Cells ◽  
Transduction Pathway ◽  
Signal Regulation

The maintenance of an orderly and controllable multicellular society depends on the communication and signal regulation among various types of biological cells. How to replicate complicate signal transduction pathways in...

scholarly journals Neuron-Specific Alterations in Signal Transduction Pathways associated with Alzheimer's Disease

2014 ◽  
Vol 40 (1) ◽  
pp. 135-142 ◽  
Author(s):  
Anne Gerschütz ◽  
Helmut Heinsen ◽  
Edna Grünblatt ◽  
Anne Kristin Wagner ◽  
Jasmin Bartl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Signal Transduction Pathways

scholarly journals CKA, a Novel Multidomain Protein, Regulates the JUN N-Terminal Kinase Signal Transduction Pathway in Drosophila

2002 ◽  
Vol 22 (6) ◽  
pp. 1792-1803 ◽  
Author(s):  
Hua-Wei Chen ◽  
Maria Julia Marinissen ◽  
Su-Wan Oh ◽  
Xiu Chen ◽  
Michael Melnick ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Sheet ◽  
Signal Transduction Pathway ◽  
Leading Edge ◽  
Genetic Screen ◽  
Signal Transduction Pathways ◽  
Dorsal Closure ◽  
Transduction Pathway ◽  
Temporal Expression ◽  
Multidomain Protein

ABSTRACT The Drosophila melanogaster JUN N-terminal kinase (DJNK) and DPP (decapentaplegic) signal transduction pathways coordinately regulate epithelial cell sheet movement during the process of dorsal closure in the embryo. By a genetic screen of mutations affecting dorsal closure in Drosophila, we have now identified a multidomain protein, connector of kinase to AP-1 (cka), that functions in the DJNK pathway and controls the localized expression of dpp in the leading-edge cells. We have also investigated how CKA acts. This unique molecule forms a complex with HEP (DJNKK), BSK (DJNK), DJUN, and DFOS. Complex formation activates BSK kinase, which in turn phosphorylates and activates DJUN and DFOS. These data suggest that CKA represents a novel molecule regulating AP-1 activity by organizing a molecular complex of kinases and transcription factors, thus coordinating the spatial-temporal expression of AP-1-regulated genes.

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.

scholarly journals The Molecule Role Ontology: An Ontology for Annotation of Signal Transduction Pathway Molecules in the Scientific Literature

2004 ◽  
Vol 5 (6-7) ◽  
pp. 528-536 ◽  
Author(s):  
Satoko Yamamoto ◽  
Takao Asanuma ◽  
Toshihisa Takagi ◽  
Ken Ichiro Fukuda
Keyword(s):  
Signal Transduction ◽  
Scientific Literature ◽  
Signal Transduction Pathway ◽  
Signal Transduction Pathways ◽  
Transduction Pathway ◽  
Abstract Concepts ◽  
Pathway Database ◽  
Sequence Identity ◽  
Concrete Objects ◽  
Single Sequence

In general, it is not easy to specify a single sequence identity for each molecule name that appears in a pathway in the scientific literature. A molecule name may stand for concepts of various granularities, from concrete objects such as H-Ras and ERK1 to abstract concepts or categories such as Ras and MAPK. Typically, the relations among molecule names derive a hierarchical structure; without a proper way to handle this knowledge, it becomes ever more difficult to develop a reliable pathway database. This paper describes an ontology that is designed to annotate molecules in the scientific literature on signal transduction pathways.

scholarly journals Inverse Molecular Docking as a Novel Approach to Study Anticarcinogenic and Anti-Neuroinflammatory Effects of Curcumin

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3351 ◽  
Author(s):  
Veronika Furlan ◽  
Janez Konc ◽  
Urban Bren
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Molecular Docking ◽  
Protein Kinase ◽  
Scientific Literature ◽  
Protein Structures ◽  
Signal Transduction Pathways ◽  
Therapeutic Effects ◽  
Mitogen Activated Protein

Research efforts are placing an ever increasing emphasis on identifying signal transduction pathways related to the chemopreventive activity of curcumin. Its anticarcinogenic effects are presumably mediated by the regulation of signaling cascades, including nuclear factor κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPK). By modulating signal transduction pathways, curcumin induces apoptosis in malignant cells, thus inhibiting cancer development and progression. Due to the lack of mechanistic insight in the scientific literature, we developed a novel inverse molecular docking protocol based on the CANDOCK algorithm. For the first time, we performed inverse molecular docking of curcumin into a collection of 13,553 available human protein structures from the Protein Data Bank resulting in prioritized target proteins of curcumin. Our predictions were in agreement with the scientific literature and confirmed that curcumin binds to folate receptor β, DNA (cytosine-5)-methyltransferase 3A, metalloproteinase-2, mitogen-activated protein kinase 9, epidermal growth factor receptor and apoptosis-inducing factor 1. We also identified new potential protein targets of curcumin, namely deoxycytidine kinase, NAD-dependent protein deacetylase sirtuin-1 and -2, ecto-5′-nucleotidase, core histone macro-H2A.1, tyrosine-protein phosphatase non-receptor type 11, macrophage colony-stimulating factor 1 receptor, GTPase HRas, aflatoxin B1 aldehyde reductase member 3, aldo-keto reductase family 1 member C3, amiloride-sensitive amine oxidase, death-associated protein kinase 2 and tryptophan-tRNA ligase, that may all play a crucial role in its observed anticancer effects. Moreover, our inverse docking results showed that curcumin potentially binds also to the proteins cAMP-specific 3′,5′-cyclic phosphodiesterase 4D and 17-β-hydroxysteroid dehydrogenase type 10, which provides a new explanation for its efficiency in the treatment of Alzheimer’s disease. We firmly believe that our computational results will complement and direct future experimental studies on curcumin’s anticancer activity as well as on its therapeutic effects against Alzheimer’s disease.

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