Hybrid Antioxidant and Metal Sequestering Small Molecules Targeting the Molecular Features of Alzheimer’s Disease

Graphical Abstract

Abstract

Alzheimer’s disease currently affects over 5.4 million Americans with $236 billion spent annually on the direct costs of patient care. Health experts expect this price tag to rise to $1.1 trillion by 2050 if intervention for disease progression is not found. Alzheimer’s disease is the sixth leading cause of death in the U.S. and the only disease in the top 10 causes of death that cannot currently be prevented or slowed. Of these deaths, two-thirds of Alzheimer’s disease victims are women. These statistics reflect an immediate worldwide need to understand the series of mechanisms that give rise to Alzheimer’s disease. With this understanding, we can develop therapeutic interventions for the disease. Here, we will discuss a selection of small molecules that have been recently developed to target the known molecular features of Alzheimer’s disease: amyloid-beta protein and oxidative stress. These potential therapeutics include small molecules inspired by early therapeutic potential demonstrated by the molecule clioquinol as well as divergent work that combines other metal-binding and antioxidant building blocks into one scaffold. The results related to the molecular features of Alzheimer’s disease will be presented.

Keywords:

• Alzheimer’s disease
• oxidative stress
• amyloid
• Aβ

FUNDING

The authors are grateful for generous financial support from TCU Andrews Institute of Mathematics & Science Education (to KG), TCU Research and Creativity Activity Grant (to KG), and INFOR Moncrief Foundation Support (to KG).

Additional information

Funding

The authors are grateful for generous financial support from TCU Andrews Institute of Mathematics & Science Education (to KG), TCU Research and Creativity Activity Grant (to KG), and INFOR Moncrief Foundation Support (to KG).