Molecular Pathways of Protein Misfolding: How Structural Failure Drives Neurodegenerative Disorders

Abstract

Proteins are essential molecules that carry out many functions within living cells, and these functions range from transmitting signals to catalyzing reactions. The proper performance of proteins within these cells relies heavily on the protein’s ability to fold into precise three-dimensional shapes. Additionally, protein’s shape determines which molecules it can bind to and how it interacts with other cellular structures. But when these proteins fail to fold correctly, they can’t perform these vital tasks, and begin forming harmful properties that accumulate and interfere with cellular health. These misfolded proteins develop the basis for many of the leading neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), and other rare prion diseases. This literature review explores the molecular pathways that direct protein folding, the biological and external factors that direct protein misfolding, and the consequences of accumulation of misfolded proteins. It examines how these misfolded proteins can disrupt cell function, how they contribute to disease progression, and why neurons are vulnerable to these changes. The paper also delves into modern diagnostic tools that can detect misfolded proteins in patients suffering with the above conditions. Additionally, this review goes into how emerging therapeutic strategies such as immunotherapy, proteostasis enhancement, artificial intelligence driven structural prediction, and others. By intertwining fundamental biochemical understandings of neurodegenerative disorders with clinical applications and relevance, this review provides a comprehensive explanation into how these structural issues arise and how they drive neurodegenerative diseases.