The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases

Abstract

The unfolded protein response (UPR) is a cellular mechanism activated by endoplasmic reticulum (ER) stress, which ranges from inhibition of protein synthesis to apoptosis. ER stress is induced in general by aggregated autologous or foreign (e.g. viral) proteins, oxidative stress, mitochondrial dysfunction, disruption of intracellular calcium, or inflammation. In patients with Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), the known stressors are aggregated amyloid-beta and superoxide dismutase (SOD-1), respectively, but autologous DNA released by trauma into the cytoplasm may also be involved in ALS. In HIV-1-associated neurocognitive disorders (HAND), ER stress is induced by HIV-1 and antiretroviral therapy. Additionally, in cases of epilepsy, ER stress has been implicated in neuronal dysfunction. In this chapter, we examine a clinical and immunologic approach to ER stress in the progression of neurological and infectious diseases. In addition, we will briefly discuss emerging treatments including omega fatty acids, progesterone, and DHA, which repair and favorably regulate UPR in some patients with neurological diseases.