Acetyl-l-carnitine and ferulic acid action in aging and neurodegenerative diseases

In 1956, Harman proposed the “free radical theory of aging” which suggested that free radicals and/or reactive oxygen species (ROS) contributed to the loss of molecular and cellular function in organisms over time (Harman 1956). This loss of function in aging is due in part to ROS exposure causing an imbalance in cellular homeostasis because the organism is not able to sufficiently scavenge free radicals. Harman’s theory has more recently been accepted as the “oxidative stress theory of aging” (Muller et al. 2007) and has been linked to disorders including cancer, atherosclerosis, stroke, and diabetes (Mariani et al. 2005). Oxidative stress also has been implicated in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) (Markesbery 1997). Because oxidative stress can affect cellular processes such as metabolism, structural integrity, inflammation, and apoptosis (Terman et al. 2006), its link with many human diseases is not surprising. As a result, many researchers have investigated the molecular mechanisms underlying oxidative stress in various model systems of aging and age-related disorders (Humphries et al. 2006; Muller et al. 2007) in order to find clues that lead to the development of therapeutic molecules. While the development/synthesis of novel compounds that are able to combat oxidative stress is necessary, there is much interest in the application of naturally occurring compounds that may also offer beneficial protection.