Atypical parkinsonism in the Caribbean island of Guadeloupe: Etiological role of the mitochondrial complex I inhibitor annonacin

Authors

  • Annie Lannuzel MD, PhD,

    Corresponding author
    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, Paris, France
    3. Department of Neurology, University Hospital, Pointe-à-Pitre, Guadeloupe, French West Indies, France
    • INSERM U679, Hôpital de la Salpêtrière, 47 bd de l'Hôpital, 75013 Paris or Department of Neurology, University Hospital, BP 465, F-97159, Pointe-à-Pitre, Guadeloupe, F.W.I., France
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  • Merle Ruberg PhD,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, Paris, France
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  • Patrick P. Michel PharmD, PhD

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, Paris, France
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  • Potential conflict of interest: None reported.

Abstract

On the French West Indian island of Guadeloupe, atypical parkinsonian patients represent two-thirds of all cases of parkinsonism, which is exceptionally frequent compared to epidemiological data from European countries where atypical parkinsonism accounts for only approximately 5% of all cases. The clinical entity was a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients were distinguished. In patients with oculomotor signs that came to autopsy, neuronal loss was found to predominate in the substantia nigra and the striatum but other brain areas were also affected, including the frontal cortex. In addition, tau-containing lesions were detected throughout the brain. Epidemiological data suggested a close association of the disease with the regular consumption of soursop, a tropical annonaceous plant. Experimental studies performed in midbrain cell cultures identified annonacin, a selective mitochondrial complex I inhibitor contained in the fruit and leaves of soursop, as a probable etiological factor. Consistent with this view, chronic administration of annonacin to rats through Alzet osmotic minipumps showed that annonacin was able to reproduce the brain lesions characteristic of the human disease. © 2008 Movement Disorder Society

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