**Abstract**

The endoplasmic reticulum (ER) is an organelle responsible for protein production in the cell and provides hemostasis in the cell. ER stress is stimulated by folded proteins, while the unfolded protein response (UPR) creates a response to ER stress and provides the cell survival. UPR modulation in mammals is provided with three major ER stress sensors, including transmembrane kinase 1, protein kinase-like ER kinase, and activating transcription factor 6. Because neurons are susceptible to misfolded proteins, severe or prolonged ER stress activates apoptotic cell death signals in the cell. Neurodegenerative diseases characterized by this condition are Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, characterized by the accumulation and aggregation of misfolded proteins. In addition, ER stress can lead to depression, schizophrenia, sleep disruption, and posttraumatic stress disorders. Neurons are highly susceptible to protein misfolding and apoptotic cell death. For this reason, UPR modulation contributes to preventing the neurodegenerative process in cells with misfolded protein folding. The relationship between ER stress, UPR, and neuropathology is significant for understanding this process. This section will discuss the effects of ER stress between UPR modulation and neurodegenerative disorders, and the histopathological changes in the mentioned neurodegenerative diseases will be mentioned.

**Keywords:** ER stress, neurodegenerative disease, apoptosis, histopathology, neuropathology

## **1. Introduction**

The endoplasmic reticulum (ER) is an organelle consisting of various structures in the form of interconnected channels and sacs in the cell [1]. The ER has various functions in the cell, such as being responsible for lipid synthesis, carbohydrate metabolism, calcium storage, and protein trafficking. Since it performs these

tasks, it is of great importance that the ER function is normal [2]. Excess nutrient intake or exceeding the working capacity of the ER for various reasons causes the accumulation of misfolded proteins in the ER, and thus the deterioration of ER homeostasis due to difficulties in meeting the demand [3]. As a result of this situation, a situation called ER stress occurs. Recently, the number of studies on this subject has been increasing due to the prevalence of ER stress. If ER stress is excessive, apoptosis occurs because the cell cannot adapt [4]. It has been determined that ER stress triggers many diseases in the organism. These diseases include obesity, diabetes, ischemia-reperfusion diseases, and neurodegenerative diseases [5]. Neurodegenerative diseases are very diverse and affect human health negatively [6]. In addition, the first is an attractive topic because the treatment of neurodegenerative diseases is limited [7]. Parkinson's, Alzheimer's, and Huntington's are among these harvests [8, 9]. In the diseases mentioned, some histopathological changes occur in various parts of the brain. Our aim in this study is to describe the definition of ER stress, the mechanisms of ER stress, the relationship of ER stress with neurodegenerative diseases, and the specific histopathological changes that occur in these diseases.
