Exploring the role of British dementia protein-2 (Bri2) and its BRICHOS domain in neurodegenerative disorders

Abstract

Protein functionality hinges on precise three-dimensional structures, while molecular chaperones orchestrate folding, proteome maintenance, and proteostasis. Recent attention has focused on BRICHOS domain from pro-proteins of pulmonary surfactant protein C (proSP-C), Bri2 and Bri3 as autonomous molecular chaperones, crucial for cellular quality control. Bri2, an integral protein, emerges with expressions ranging from the central nervous system to cancer and lung diseases and exhibits proficiency in combating amyloid aggregation, a hallmark of neurodegenerative disorders like Alzheimer's. The capability of Bri2-BRICHOS to shield aggregation-prone regions, unveiling its role as an intramolecular guardian. In this review, we explore the structure and function of BRI2 and its relation to neurodegenerative diseases, as well as the structural complexities, functional landscapes, and implications of BRICHOS domains in diverse neurodegenerative disorders. Furthermore, it sheds light on Bri2-BRICHOS as a possible candidate for therapeutic approaches in protein aggregation disorders.