ER Stress Signaling in Alzheimer's Disease: Molecular Mechanisms and Therapeutic Implications

ER Stress Signaling in Alzheimer's Disease: Molecular Mechanisms and Therapeutic Implications

Md. Motiar Rahman (Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), China), Looniva Shrestha (Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), China) and Mst Ara Gulshan (Graduate School of Innovative Life Science, University of Toyama, Japan)
Copyright: © 2020 |Pages: 32
DOI: 10.4018/978-1-7998-1317-0.ch007

Abstract

Alzheimer's disease (AD) is the most common etiology of dementia amongst aged individuals and a principal public health-related abnormality. It is considered as a multifactorial disorder, with no particular origin identified, and also some modifiable, as well as non-modifiable threats are correlated with its progression and development. The endoplasmic reticulum (ER) stress response is considered as a key process in the pathogenesis of AD. In this chapter, the authors present a summary of related transmembrane kinase proteins responsible for the onset of AD as well as show the interrelationship between ER stress and AD. Finally, the authors demonstrate the therapeutics intervention for AD diagnosis by highlighting the current practices to advance novel therapies.
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Introduction

Alzheimer’s disease (AD) is an extremely severe or irreversible, and radical disease of the brain that progressively devastates memory as well as thinking abilities and, ultimately, the capability to perform the easiest works (Mann, 1996; Norfray and Provenzale, 2004; Strassnig and Ganguli, 2005). It is known that AD is the utmost basis for developing dementia amongst elderly peoples (Korolev, 2014). AD is currently known as the 5th prominent cause of mortality in the US among 65 years or elderly individuals (Heron, 2013), and around $200 billion are exhausted every year on uninterrupted care of patients with progressive dementia. Worldwide, it is projected that about 35 million of populations possess either the symptoms of AD or any forms of dementia, and around 65 million are anticipated to develop dementia by 2030 and 115 million by 2050, respectively (Prince et al., 2013).

AD was coined after the name of Dr. Alois Alzheimer, a German psychiatrist, and neurologist. In 1906, he observed alterations in the tissue of the brain of a woman who had just died of abnormal brain disorder along with indications involved memory damage, vocal complications, and unusual manner (Alzheimer, 1907). Dr. Alzheimer then investigated her brain and uncovered several abnormal clumps (more familiar as amyloid plaques) and tangled bundles of fibers (familiar as tau or neurofibrillary tangles), which are still considered as some of the prime features of AD (Korolev, 2014). Besides, impairment of contacts between nerve cells observes in the AD brain. Generally, neurons pass a signal between various portions of the brain, and conversely, from the brain tissues to various organs of the body. Several other intricated brain alterations are assumed to govern a substantial function in AD, too. This loss primarily looks to develop in the brain hippocampus, responsible for growing memories. Since neurons die, other portions of the brain are agitated (Devanand et al., 2007; Jack et al., 1997). At the last step of AD, destruction is extensive, and brain tissue has disappeared drastically.

Endoplasmic reticulum (ER) is the major component for efficient protein folding and quality control that are prerequisites to support cellular biochemical reactions. But, ER stress and UPR are indulged in the incidence of synaptic dysfunction in prion-related abnormalities and AD. In normal conditions, ER maintains protein maturation, calcium balance and expression of certain altered proteins or vesicles transport (ER-Golgi apparatus). However, under ER stress, cells stimulate a passive response, the unfolded protein response (UPR), are responsible to enhance protein folding ability, in addition to activating the capacity of quality control as well as protein degeneration pathway to diminish the unfolded protein (UP) load (Walter and Ron, 2011). Under extreme ER stress conditions, the UPR turns its pathway toward apoptosis by initiating intricate pro-apoptotic pathways (Urra et al., 2013).

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