The Role of PERK in Understanding Development of Neurodegenerative Diseases

• Main Authors: Garrett Dalton Smedley, Keenan E. Walker, Shauna H. Yuan
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Molecular Sciences
• Subjects: unfolded protein response; endoplasmic reticulum stress; PERK; neurodegeneration; tauopathy; therapy
• Online Access: https://www.mdpi.com/1422-0067/22/15/8146
• ISSN: 1661-6596; 1422-0067

Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER kinase (PERK) comprises one of three unfolded protein response pathways in which cells attempt to manage cellular stress. However, because of its role in the cellular stress response and the far-reaching implications of this pathway, error within the PERK pathway has been shown to lead to a variety of pathologies. Genetic and clinical studies show a correlation between failure of the PERK pathway in neural cells and the development of neurodegeneration, but the wide array of methodology of these studies is presenting conflicting narratives about the role of PERK in these affected systems. Because of the connection between PERK and pathology, PERK has become a high value target of study for understanding neurodegenerative diseases and potentially how to treat them. Here, we present a review of the literature indexed in PubMed of the PERK pathway and some of the complexities involved in investigating the protein’s role in the development of neurodegenerative diseases as well as how it may act as a target for therapeutics.