N-Acetylcysteine: A Natural Antidote for Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most devastating age-related dementia, which has no effective treatment. Since the pathological hallmarks of AD brains are Aβ plaques and intra-neuronal tau-containing neurofibrillary tangles, most therapeutic approaches, including immunotherapy, are based on the concept that the accumulation of these proteins produces neuronal damage and death. Alternatively, it has been proposed that reactive species can cause oxidative damage including mitochondrial disruption, contributing to AD initiation and progression. Can these cellular dysfunctions be linked by a common pathogenic mechanism susceptible to therapy with the natural compound N-acetylcysteine? A cellular cysteine network (CYSTEINET) has been proposed as a functional and structural matrix of interconnected sensitive cysteine-containing proteins (SCCPs) that in conjunction with reactive species and the cysteine/glutathione cycles can regulate the bioenergetic metabolism, the redox homeostasis, and the cellular survival through different pathways that bear the same regulatory thiol radical. The present paper proposes that cysteinet is impaired in Alzheimer's disease resulting in a functional and structural deregulation of the matrix of interconnected cysteine-containing proteins that result in misfolding, aggregation and accumulation of specific toxic proteins. In this context, the role of N-acetylcysteine to prevent and restore cysteinet deregulation in AD development and progression is discussed.