Dementia, Dopamine, and Medicinal Chemistry Drug Design

Abstract

Neurodegenerative and neurological diseases that afflict those in mid to late life have steadily become a common cause of mortality worldwide as elderly populations have continued to grow. Epidemiological reviews of these neurodegenerative diseases show that associated deaths have increased within the last 25 years. Evidence supports neurodegenerative diseases, especially Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are linked to dementia symptoms in afflicted patients. Although AD and PD have different etiologies, and have some pathological differences, they also share similar neurodegenerative sequela, such as glial activation and dopamine (DA) dysregulation. The aim of this review is to discuss basic AD and PD pathophysiology and the role of DA regulation in these two neurodegenerative diseases. This review will then cover the current state-of-the-art treatments for AD and PD, with a focus on DA regulation. This review will also discuss novel medicinal chemistry approaches for central nervous system DA modulation, which may be therapeutically advantageous in AD and PD treatment. Finally, this review will discuss how targeting translocator protein (TSPO), a protein found within immune cells, may be a beneficial approach for treating aberrant glial cell activation and neuroinflammation.