Multifarious Role of BAG3 in Neurodegenerative Disorders

Multifarious Role of BAG3 in Neurodegenerative Disorders

Sujata Basu (Enago-Publication Support, Crimson Interactive Pvt. Ltd., India), Manisha Singh (Jaypee Institute of Information Technology, India), Mansi Verma (Jaypee Institute of Information Technology, India) and Rachana R. (Jaypee Institute of Information Technology, India)
Copyright: © 2020 |Pages: 21
DOI: 10.4018/978-1-7998-1317-0.ch010

Abstract

The glial cells along with cells of hematopoietic origin and microvascular endothelia work together to maintain the normal development and/or functioning of the nervous system. Disruption in functional coordination among these cells interrupts the efficiency of the nervous system, leading to neurodegeneration. Various proteins in the nerve cells maintain the normal signaling mechanism with these cells and throughout the body. Structural/functional disorganization of these proteins causes neurodegenerative disorders. The molecular mechanisms involved in these phenomena are yet to be explored extensively from therapeutic perspectives. Through this chapter, the authors have elaborated on less known protein Bcl-2 associated athanogene 3 (BAG3) involved in neurodegeneration. They have explored BAG3 protein and its role in neurodegeneration, protein homeostasis, its mechanism of action, its uses as a drug target, and its uses as a possible diagnostic marker of neurodegeneration.
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Introduction

In today's world of medical advancement, state-of-art medical technology has advanced the chances of life expectancy on an average scale in mankind. In spite of many improvements in this sphere, medical science is still in the struggling era of controlling aging. The cause behind this tussle between medical science and control of the aging phenomenon lies in several concerns, including dealing with neurodegenerative disorders (NDDs). The progression of neurological ailment from its initial stage to final is linked to injuries in the brain, its associated neurons and the neuronal circuit in our body (Pekna, 2012). During neurodegeneration, a progressive deterioration of neuronal structures and functions occurs which ultimately leads to cognitive disability and dementia (Ramanan and Saykin, 2013). Various proteins play unique functional roles in different regions of healthy neurons while maintaining several functions like neuronal migration and differentiation, neuronal growth, and organized neural connectivity from axon to synapse (Tau and Peterson, 2010; de Wit et al., 2011). These include proteins involved in ion channels, proton pump, scaffolding, structural integrity of the cell and proteins responsible for postsynaptic density and anti-apoptosis (Vinothkumar and Henderson, 2010; Cherry, 2018).

The microglia (myeloid cells of the hematopoietic system) or astroglia and oligodendrocytes (neuroepithelial progenitor cells of hematopoietic origin), along with glial cells, and microvascular endothelia, work together to maintain the normal development and/or functioning of the nervous system (Eglitis and Mezey, 1997). An interruption in the coordinated functioning of these cells disrupts the functional ability of the nervous system, which thereby can lead to neurodegeneration (National Research Council, 1989). The list of neurodegenerative disorders is long, however, only a few of them have drawn the attention of researchers. These include Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), etc. The other neurodegenerative disorders are equally devastating; however, their exact cause remained essentially unexplored so far. Several scientists have attempted to examine the molecular interplays in cells for an individual neurodegenerative disease, at pathway level as well as, at the genetic level (Arneson et al., 2018; Narayanan, 2015) which are genetically controlled in neuronal cells. Though the neurodegenerative disorders differ from each other in terms of their symptoms and treatment modality yet, they are likely to be interconnected in some way through a dynamic molecular interplay inside the cells.

The modulation of neurodegenerative processes has been forecasted to occur due to strong interplay among intracellular mechanisms, local tissue environment, systemic environment, and mechanisms associated with cell development and aging as shown in Figure 1. This chapter aims to present the molecular interplay in neuronal cells under stressed conditions, with a focus on the upcoming possible role player, biomarker and drug target Bcl2-associated athanogene 3 (BAG3). The literature explored to predict the role of BAG3 in the prevention of cellular stress. Also, the probable mechanism of BAG3 to regain the protein homeostasis of neuronal cells through close interaction with various chaperones, anti-apoptotic factors, and other cellular components/proteins/organelles is discussed.

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