Decrypting the potential role of α-lipoic acid in Alzheimer's disease

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases with motor disturbances, cognitive decline, and behavioral impairment. It is characterized by the extracellular aggregation of amyloid-β plaques and the intracellular accumulation of tau protein. AD patients show a cognitive decline, which has been associated with oxidative stress, as well as mitochondrial dysfunction. Alpha-lipoic acid (α-LA), a natural antioxidant present in food and used as a dietary supplement, has been considered a promising agent for the prevention or treatment of neurodegenerative disorders. Despite multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects, to date only a few studies have examined its effects in humans. Studies performed in animal models of memory loss associated with aging and AD have shown that α-LA improves memory in a variety of behavioral paradigms. Furthermore, molecular mechanisms underlying α-LA effects have also been investigated. Accordingly, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies. In addition, it has been shown that α-LA reverses age-associated loss of neurotransmitters and their receptors. The review article aimed at summarizing and discussing the main studies investigating the neuroprotective effects of α-LA on cognition as well as its molecular effects, to improve the understanding of the therapeutic potential of α-LA in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with α-LA.