Ghosh Priyam, Mukhopadhyay Sayantani, Kandasamy Thirukumaran, Mondal Subrata, Ghosh Siddhartha Sankar, Iyer Parameswar Krishnan
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Center for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
J Mater Chem B. 2025 Jan 22;13(4):1412-1423. doi: 10.1039/d4tb01740d.
Understanding molecular motifs that can interfere with amyloid fibrillation through non-covalent interactions is essential for addressing abnormal protein aggregation and associated human diseases. The pursuit of efficient diagnostic and treatment approaches for Alzheimer's disease (AD) has resulted in the development of M8HQ, a multifaceted small molecule turn-on probe derived from 8-hydroxyquinoline with versatile capabilities. M8HQ shows a strong affinity for amyloid beta (Aβ) fibrils, and its ability to target lysosomes enhances therapeutic precision by localizing within these organelles. This localization is essential for restoring cellular balance and maintaining LAMP1 expression, both of which are crucial for addressing AD. It also displays the ability to disaggregate Aβ fibrils and inhibit their formation, thus addressing therapeutic processes in AD progression. M8HQ further blocks reactive oxygen species (ROS)-mediated apoptosis, providing neuroprotective effects. Additionally, it chelates metal ions like Cu(II) and Fe(III), mitigating metal-induced aggregation and oxidative stress. Molecular docking and simulation studies have elucidated the interactions between M8HQ and Aβ, confirming its binding efficacy and stability. These combined properties highlight M8HQ's potential as a comprehensive diagnostic and therapeutic tool for AD.
