Multifunctional Fluorescent Probes Unveiling Complex Pathways in Alzheimer’s Disease Pathogenesis

Abstract

Alzheimer’s disease (AD) is a complex neurological disorder with a progressive nature, posing challenges in diagnosis and treatment. It is characterized by the formation of Aβ plaques and neurofibrillary tangles (NFTs), which have been the focus of clinical diagnosis and treatment. Despite decades of research, the elusive nature of AD has made it difficult to develop widely recognized diagnostic and treatment methods. However, recent advances have led to new diagnostic and therapeutic techniques targeting Aβ and tau. These technologies aim to address gaps in our understanding by targeting biomarkers using multifunctional fluorescent organic-molecule-based theranostics. There is a leading hypothesis that Aβ and its oligomers are crucial pathogenic features in AD-afflicted brains. Metals found in Aβ plaques have been linked to AD, contributing to oxidative stress and stabilizing toxic Aβ oligomers. Drug research is addressing AD’s diverse toxicity, including protein aggregation, metal toxicity, oxidative stress, mitochondrial damage, and neuroinflammation. Drug development is adopting multifaceted approaches, focusing on the intricate interaction of AD contributors. Diverse diagnostic techniques and innovative drug development tactics are crucial for AD diagnosis and therapy advances.

This Account is focused on analyzing the interaction between fluorescent molecular probes in the context of AD theranostics. It explores their design methods, imaging techniques, and therapeutic applications to develop innovative approaches for diagnosing and treating AD, thereby contributing to the advancement of precision medicine in neurodegenerative disorders. The first section explains the pathological factors associated with AD, while the second part discusses recently identified multifunctional fluorescent compounds as therapeutic and diagnostic targets. We also delve into the multifunctional probes developed in our laboratory over the past decade for the purpose of AD theranostics. The subsequent section covers small molecule and conjugated polymer (CP) chemistry, design, and functions. Our research aims to shed light on AD development by studying the link between Aβ, metal ions, and particularly metal-Aβ interactions. We utilize multifunctional fluorescent molecular probes to target metal-Aβ species, modulate interaction, and guide aggregation into nontoxic, off-pathway aggregates. These multipotent ligands reduce oxidative stress by preventing the production of reactive intermediate species (RIS) from redox-active metal-Aβ. Ongoing research aims to enhance fluorescent compounds for early and accurate detection of AD and to prevent its associated causes. We also explore current challenges and potential methods for developing multifunctional probes for AD theranostics. This Account aims to aid readers in understanding the multifaceted nature of AD and the development of novel multifunctional molecules that target its multifaceted toxicity.