The Role of ß-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 ß-carboline alkaloids (ßCAs), might be generated through Maillard-type reaction. ßCAs are molecules which are members of a large group of heterocyclic amines (HCAs, the so-called products of cooking meat). ßCAs 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 ßCAs remains currently the main experimental model of ET. We review the pathogenesis of ET, with a focus on the biochemistry of ßCAs, 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 ßCAs in humans.