title: Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae?
abstract: An abnormally frequent atypical levodopa-unresponsive, akinetic-rigid syndrome with some similarity to PSP was identified in the Caribbean island Guadeloupe, and was associated with the consumption of plants of the Annonacea family, especially Annona muricata (corossol, soursop) suggesting a possible toxic etiology. Annonaceae contain two groups of potential toxins, alkaloids and acetogenins. Both alkaloids and annonacin, the most abundant acetogenin, were toxic in vitro to dopaminergic and other neurons. However we have focused our work on annonacin for two reasons: (1) annonacin was toxic in nanomolar concentrations, whereas micromolar concentrations of the alkaloids were needed, (2) acetogenins are potent mitochondrial poisons, like other parkinsonism-inducing compounds. We have also shown that high concentrations of annonacin are present in the fruit or aqueous extracts of the leaves of A. muricata, can cross the blood brain barrier since it was detected in brain parenchyma of rats treated chronically with the molecule, and induced neurodegeneration of basal ganglia in these animals, similar to that observed in atypical parkinsonism. These studies reinforce the concept that consumption of Annonaceae may contribute to the pathogenesis of atypical parkinsonism in Guadeloupe.
authors.affiliation: Department of Neurology, University Hospital, Pointe-a-Pitre, Guadeloupe, France. annie.lannuzel@wanadoo.fr
authors.forename: A
authors.initials: A
authors.lastname: Lannuzel
authors.forename: G U
authors.initials: GU
authors.lastname: Höglinger
authors.forename: P
authors.initials: P
authors.lastname: Champy
authors.forename: P P
authors.initials: PP
authors.lastname: Michel
authors.forename: E C
authors.initials: EC
authors.lastname: Hirsch
authors.forename: M
authors.initials: M
authors.lastname: Ruberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000302:isolation & purification / Q000633:toxicity; D000818:Animals; D029061:Annonaceae / Q000009:adverse effects*; D002478:Cells, Cultured; D005638:Fruit; D005663:Furans / Q000302:isolation & purification / Q000633:toxicity; D029001:Herbal Medicine; D007783:Lactones / Q000302:isolation & purification / Q000633:toxicity; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D017072:Neostriatum / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000453:epidemiology; D010936:Plant Extracts / Q000009:adverse effects; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D013378:Substantia Nigra / Q000473:pathology; D014900:West Indies / Q000453:epidemiology
chemical_list: D000470:Alkaloids; D005663:Furans; D007783:Lactones; D010936:Plant Extracts; C053442:annonacin; D000255:Adenosine Triphosphate