Protein misfolding and neurodegeneration: Mechanisms, implications, and therapeutic strategies

Protein misfolding and aggregation play a pivotal role in the development of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's disease, and other related disorders. Proper protein folding is essential for cellular function, but due to the complexity of the folding process and external factors like genetic mutations, oxidative stress, and aging, misfolding is inevitable. These misfolded proteins often aggregate into toxic forms that disrupt cellular processes, leading to neuronal damage and cognitive decline. This chapter provides a comprehensive overview of molecular mechanisms behind protein misfolding, highlighting how these abnormal structures contribute to neurodegeneration. It also explores the role of the proteostasis network and its therapeutic potential in alleviating these processes. Focusing on multitarget therapeutic strategies, the chapter offers insights into promising approaches for addressing the root causes of neurodegenerative diseases while identifying key research gaps that could shape future treatment developments. By blending current knowledge with emerging therapeutic directions, this chapter provides a comprehensive and engaging perspective on combating the challenges of protein misfolding in neurodegeneration.