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Acetogenins AND Parkinson's disease

Dominique Caparros-Lefebvre, John Steele
INTRODUCTION: : On Guadeloupe, atypical parkinsonism is abnormally frequent, and represents 75% of progressive parkinsonism while Parkinson's disease (PD) accounts for only 25%, which is an inversed percentage in comparison with Europe. Herbal tea made with Annonaceae leaves (containing benzyltetrahydroisoquinolines (Be-TIQ), tetrahydroprotoberberines (THPB) and acetogenins (potent mitochondrial complex I inhibitors) are commonly used on Guadeloupe. CLINICAL STUDY: : Of 265 patients studied on Guadeloupe, 66 (25%) had PD, and 199 (75%) had atypical parkinsonism...
May 2005: Environmental Toxicology and Pharmacology
R Guillopé, M Escobar-Khondiker, V Guérineau, O Laprévote, G U Höglinger, P Champy
Guadeloupean Parkinsonism has been linked epidemiologically to the consumption of Annonaceae fruits. These were proposed to be etiological agents for sporadic atypical Parkinsonism worldwide, because of their content of neurotoxins such as isoquinolinic alkaloids and Annonaceous acetogenins. The pulp of Annona cherimolia Mill. from Spain was screened for these toxic molecules using Matrix-Assisted Laser Desorption Ionisation - Time of Flight mass spectrometry (MALDI-TOF MS) and it was found not to be a source of exposure...
December 2011: Phytotherapy Research: PTR
Valérie Cochen De Cock, Annie Lannuzel, Stéphane Verhaeghe, Emmanuel Roze, Merle Ruberg, Jean Philippe Derenne, Jean Claude Willer, Marie Vidailhet, Isabelle Arnulf
STUDY OBJECTIVE: To describe sleep characteristics and rapid eye movement (REM) sleep behavior disorder in patients with Guadeloupean atypical parkinsonism (Gd-PSP), a tauopathy resembling progressive supranuclear palsy that mainly affects the midbrain. It is possibly caused by the ingestion of sour sop (corossol), a tropical fruit containing acetogenins, which are mitochondrial poisons. DESIGN: Sleep interview, motor and cognitive tests, and overnight videopolysomnography...
August 2007: Sleep
A Lannuzel, G U Höglinger, P Champy, P P Michel, E C Hirsch, M Ruberg
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...
2006: Journal of Neural Transmission. Supplementum
Dominique Caparros-Lefebvre, John Steele, Yaichiro Kotake, Shigeru Ohta
Over the last 60 years an abnormally high prevalence of atypical Parkinsonism has been reported in 5 different geographic isolates. It was first described on Guam, later in New Guinea and in the Kii peninsula, on Guadeloupe, and in New Caledonia. We investigated the phenotype of atypical Parkinsonism in three of these foci and observed several similarities with dementia in most and amyotrophic lateral sclerosis in some. This disappearance of this disease in two places--Guam and New Guinea--suggested an environmental origin which has not been clarified before the disease ended...
October 2006: Movement Disorders: Official Journal of the Movement Disorder Society
Dominique Caparros-Lefebvre, Andrew J Lees
We characterize the clinical features of Parkinson's syndrome on Guadeloupe and describe possible environmental causes. Consecutive patients who were referred to the University Hospital at Pointe a Pitre with parkinsonism from September 1996 to May 2002 were included. All cases were examined in a standardized manner by a neurologist with a special interest in movement disorders and independently by 3 external movement disorders specialists, using standard operational clinical diagnostic criteria. The subjects were 265 patients with Parkinson's syndrome living on Guadeloupe, four fifths of whom had been referred by primary care physicians and one fifth by neurologists...
August 2005: Movement Disorders: Official Journal of the Movement Disorder Society
Pierre Champy, Günter U Höglinger, Jean Féger, Christophe Gleye, Reynald Hocquemiller, Alain Laurens, Vincent Guérineau, Olivier Laprévote, Fadia Medja, Anne Lombès, Patrick P Michel, Annie Lannuzel, Etienne C Hirsch, Merle Ruberg
In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%...
January 2004: Journal of Neurochemistry
Y Kotake, S Ohta
This review focuses on the mechanisms of action and the injurious effect of complex I inhibitors, of which 1-methyl-4-phenylpyridinium ion (MPP(+)) is a well studied example. These compounds can be divided into two groups, i.e. competitive inhibitors with respect to ubiquinone, such as piericidine A, and non-competitive inhibitors such as rotenone. Complex I inhibitors such as MPP(+) have been reported to induce anatomical, behavioral, and biochemical changes similar to those seen in Parkinson's disease, which is characterized by nigrostriatal dopaminergic neuro-degeneration...
December 2003: Current Medicinal Chemistry
A Lannuzel, P P Michel, G U Höglinger, P Champy, A Jousset, F Medja, A Lombès, F Darios, C Gleye, A Laurens, R Hocquemiller, E C Hirsch, M Ruberg
The death of dopaminergic neurons induced by systemic administration of mitochondrial respiratory chain complex I inhibitors such as 1-methyl-4-phenylpyridinium (MPP(+); given as the prodrug 1-methyl-1,2,3,6-tetrahydropyridine) or the pesticide rotenone have raised the question as to whether this family of compounds are the cause of some forms of Parkinsonism. We have examined the neurotoxic potential of another complex I inhibitor, annonacin, the major acetogenin of Annona muricata (soursop), a tropical plant suspected to be the cause of an atypical form of Parkinson disease in the French West Indies (Guadeloupe)...
2003: Neuroscience
Dominique Caparros-Lefebvre, Nicolas Sergeant, Andrew Lees, Agnes Camuzat, Susan Daniel, Annie Lannuzel, Alexis Brice, Eduardo Tolosa, Andre Delacourte, Charles Duyckaerts
An unusually high frequency of atypical Parkinson syndrome has been delineated over the last 5 years in the French West Indies. Postural instability with early falls, prominent frontal lobe dysfunction and pseudo-bulbar palsy were common and three-quarters of the patients were L-dopa unresponsive. One-third of all patients seen had probable progressive supranuclear palsy (PSP). This new focus of atypical parkinsonism is reminiscent of the one described in Guam and may be linked to exposure to tropical plants containing mitochondrial complex I inhibitors (quinolines, acetogenins, rotenoids)...
April 2002: Brain: a Journal of Neurology
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