Chapter 16: Multifunctional Inhibitors of Multifaceted Aβ Toxicity of Alzheimer's Disease Check Access

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multifaceted toxicity. Amyloid β (Aβ) peptides and their aggregation species (oligomers, protofibrils, and fibrils) are considered as the hallmarks of AD pathology. The multifactorial nature of AD comprises multiple toxicity routes including Aβ aggregation and associated toxicity, metal toxicity, oxidative stress, biomolecules damage, membrane toxicity, mitochondrial dysfunction, and neuroinflammation among others. The therapeutic candidates developed to ameliorate amyloid toxicity showed moderate to poor success, as these approaches mostly targeted individual disease routes ignoring the multifaceted toxicity of AD. These failures raised concerns and encouraged researchers to develop multifunctional agents to tackle the multifaceted amyloid toxicity of AD. In this chapter, we present design and development of small molecule, natural product-derived, peptide and polymer based multifunctional modulators and their in vitro, in cellulo, and in vivo efficacy to ameliorate multifaceted Aβ toxicity of AD.