Abstract

Protein folding is a fundamental biological process essential for cellular function and life itself. The correct three-dimensional conformation of proteins determines their biological activity, enabling them to perform diverse cellular roles from catalysis to structural support. However, when proteins misfold and aggregate, they can lead to devastating neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). These misfolded protein aggregates cause cellular toxicity and contribute to cellular proteostatic collapse, ultimately resulting in neuronal dysfunction and death. This review aims to elucidate the molecular pathways governing protein folding and misfolding, examining how these processes contribute to neurodegenerative pathology. We explore the role of molecular chaperones in maintaining protein homeostasis and discuss emerging therapeutic approaches targeting protein quality control mechanisms. Recent advancements in CRISPR/Cas9 technology are revolutionizing research in addressing protein misfolding mechanisms, while smart imaging probes are facilitating early diagnosis and drug discovery. Understanding these molecular mechanisms is crucial for developing effective treatments for age-related neurodegenerative diseases that increasingly burden our aging population.