The Role of β-Carboline Alkaloids in the Pathogenesis of Essential Tremor

Essential tremor (ET) is one of the most prevalent neurological disorders in the world. Environmental factors have been implicated in the pathogenesis of ET. In particular, epidemiological studies have suggested that neurotoxic agents, especially beta-carboline alkaloids (beta CAs), might be generated through Maillard-type reaction. beta CAs are molecules which are members of a large group of heterocyclic amines (HCAs, the so-called products of cooking meat). beta CAs are highly tremorogenic in animals, producing a marked generalized action tremor soon after systemic administration in a wide range of laboratory animals such as mice, rats and monkeys. Administration of beta CAs remains currently the main experimental model of ET. We review the pathogenesis of ET, with a focus on the biochemistry of beta CAs, their occurrence and biological activity, their endogenous biosynthesis, their formation in food, their toxicokinetics and their neurotoxicity. We highlight open questions regarding the effects of beta CAs in humans.