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Investigating the Signal Transduction Pathway Error Present in those with Alzheimer's Disease

Summary

Normal Signal Transduction Pathway

The mitogen-activated protein kinase (MAPK) signal transduction is carried out in the form of a cascade of 3 kinases. The signaling cascade is involved in coordinating crucial cellular functions. MAPK has been demonstrated to phosphorylate and regulate numerous cellular proteins, including transcription factors and other protein kinases. MAPK is phosphorylated and activated by MAPKK, and then transferred into the nucleus.

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Wnt signaling is one of the most important developmental signaling pathways that control cell fate decisions and tissue patterning during early embryonic and later development. It is activated by highly conserved Wnt proteins that are secreted as glycoproteins and act as morphogens to form a concentration gradient across a developing tissue. Wnt proteins regulate transcriptional and posttranscriptional processes depending on the distance of their origin and activate distinct intracellular cascades. Mutations in this signaling can lead to many long term diseases such as Alzheimer's.
 

Normal STP
Introduction

Introduction to ALzheimer's Disease

Alzheimer's Error

Alzheimer's affects a person’s memory, thinking, and behavior and is the most common cause of dementia or memory loss. Alzheimer's can be caused by plaques and tangles in the brain, responsible for damaging and killing nerve cells. It affects the activity of brain chemicals, called neurotransmitters which produce flawed signaling, therefore brain messages are lost. Alzheimer's eventually shrinks parts of brain, commonly memory which can also harm the brain’s ability to create new memories. Abnormal protein build up near or in brain cells is one main cause of the disease.

Alzheimer's Signal Transduction Pathway Error

In Alzheimer's abnormal levels of beta-amyloid 42 naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function. Abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. 

 

These tangles block the neuron’s transport system, which harms the STP communication between neurons. As neurons are injured and die throughout the brain, connections between networks of neurons may break down, and many brain regions begin to shrink.

 

Wnt participates in tau phosphorylation and processes of learning and memory. Inhibition of Wnt signaling results in memory loss, tau (proteins abundant in the neurons of the nervous system) phosphorylation, and Amyloid Beta formation and aggregation (plaques are formed) which disrupt cell function. Wnt dysfunction can accelerate the onset of Alzheimer's Disease

Data and Results

Sources

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“Alzheimer's Disease Signaling Pathway.” Proteintech Group, Aug. 2017, www.ptglab.com/news/blog/alzheimers-disease-signaling-pathway/. 
Felice, Fernanda G. De, et al. “How Does Brain Insulin Resistance Develop in Alzheimer's Disease?” Alzheimer's & Dementia, No Longer Published by Elsevier, 14 Feb. 2014, www.sciencedirect.com/science/article/pii/S155252601302918X. 
Kablar Natasa. "Signalling Pathways Coupling in Alzheimer Disease". ECronicon, January 2019, https://www.ecronicon.com/ecpp/pdf/ECPP-08-00410.pdf
“What Happens to the Brain in Alzheimer's Disease?” National Institute on Aging, U.S. Department of Health and Human Services, May 2017, www.nia.nih.gov/health/what-happens-brain-alzheimers-disease. 
Tapia-Rojas, Cheril, and Nibaldo C Inestrosa. “Loss of Canonical Wnt Signaling Is Involved in the Pathogenesis of Alzheimer's Disease.” Neural Regeneration Research, Medknow Publications & Media Pvt Ltd, Oct. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6128062/. 
“Three Stages of Cell Signaling.” WINNACUNNET BIOLOGY, 3 Apr. 2016, croteaubio.wordpress.com/ap-bio-tutorials/tutorials/three-stages-of-cell-signaling/. 
Colbert, Treacy. “What Does Alzheimer's Do to the Brain?” Healthline, Healthline Media, 1 Dec. 2017, www.healthline.com/health/alzheimers-and-brain#inflammation. 

©2021 by Anika Chandwani

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