Ferulic acid: A natural antioxidant with application towards neuroprotection against Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people worldwide. AD pathology is mainly caused due to the deposition of amyloid beta (Aβ) peptide and upsurge of oxidative stress, the two major factors responsible for AD occurrence and progression. The current treatment strategies available are merely effective and lack long-term benefits against this disease, which necessitates the need for the use of antioxidants for managing/preventing AD pathology. Ferulic acid (FA), a natural antioxidant found in various fruits (such as orange and grapefruit), vegetables (such as broccoli and tomato), coffee beans and barley used in beverages (such as coffee and beer), can be utilized as a natural source of antioxidants against AD. Several studies have pointed towards the protective effects of FA against AD in vitro as well as in vivo. The antioxidant defence system is known to be compromised in AD, whereas the use of FA has been shown to restore the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and heme oxygenase-1 (HO-1). FA has also been shown to destabilize the preformed Aβ fibrils both in vitro and in vivo. Several studies have pointed towards the neuroprotective role of FA through modulating the expression of several key proteins such as p38, Hsp70, ERK1/2, foxo3a and Akt, thus playing a key role towards neuroprotection. In addition, FA is also reported to inhibit the inflammatory responses induced by lipopolysaccharides (LPS) in microglia and also shown to modulate the β-secretase activity and improved AD-like pathology in transgenic mice model study. Inhibition of acetylcholinesterase (AChE) activity and restoration of mitochondrial membrane potential by FA has also been reported. Taken together, it is advocated that the use of FA in routine diet may effectively lower the risk of developing AD and can play an important role in managing the disease. In this book chapter, we will try to document and summarize the structure and functional aspects of FA along with the known benefits of it as a neuroprotective agent against AD.