Phytochemical based Modulation of Endoplasmic Reticulum Stress in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a severe progressive neurodegenerative condition that shows misfolding and aggregation of proteins contributing to a decline in cognitive function involving multiple behavioral, neuropsychological, and cognitive domains. Multiple epi (genetic) changes and environmental agents have been shown to play an active role in ER stress induction. Neurodegeneration due to endoplasmic reticulum (ER) stress is considered one of the major underlying causes of AD. ER stress may affect essential cellular functions related to biosynthesis, assembly, folding, and post-translational modification of proteins leading to neuronal inflammation to promote AD pathology. Treatment with phytochemicals has been shown to delay the onset and disease progression and improve the well-being of patients by targeting multiple signaling pathways in AD. Phytochemical's protective effect against neuronal damage in AD pathology may be associated with the reversal of ER stress and unfolding protein response by enhancing the antioxidant and anti-inflammatory properties of the neuronal cells. Hence, pharmacological interventions using phytochemicals can be a potential strategy to reverse ER stress and improve AD management. Towards this, the present review discusses the role of phytochemicals in preventing ER stress in the pathology of AD.

Keywords: Alzheimer's disease; Antioxidant; Apoptosis; Endoplasmic reticulum stress; Neuronal cell death; Phytochemicals; Reactive oxygen species; Unfolded protein response.