Isolation of various forms of sterol β-d-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex
Identifieur interne : 003074 ( Main/Curation ); précédent : 003073; suivant : 003075Isolation of various forms of sterol β-d-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex
Auteurs : I. Khabazian [Canada] ; J. S. Bains [Canada] ; D. E. Williams [Canada] ; J. Cheung [Canada] ; J. M. B. Wilson [Canada] ; B. A. Pasqualotto [Canada] ; S. L. Pelech [Canada] ; R. J. Andersen [Canada] ; Y.-T. Wang [Canada] ; L. Liu [Canada] ; A. Nagai [Canada] ; S. U. Kim [Canada] ; U-K. Craig ; C. A. Shaw [Canada]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 2002.
Descripteurs français
- Pascal (Inist)
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Abstract
The factors responsible for ALS-parkinsonism dementia complex (ALS-PDC), the unique neurological disorder of Guam, remain unresolved, but identification of causal factors could lead to clues for related neurodegenerative disorders elsewhere. Earlier studies focused on the consumption and toxicity of the seed of Cycas circinalis, a traditional staple of the indigenous diet, but found no convincing evidence for toxin-linked neurodegeneration. We have reassessed the issue in a series of in vitro bioassays designed to isolate non-water soluble compounds from washed cycad flour and have identified three sterol β-D-glucosides as potential neurotoxins. These compounds give depolarizing field potentials in cortical slices, induce alterations in the activity of specific protein kinases, and cause release of glutamate. They are also highly toxic, leading to release of lactate dehydrogenase (LDH). The aglycone form, however, is non-toxic. NMDA receptor antagonists block the actions of the sterol glucosides, but do not compete for binding to the NMDA receptor. The most probable mechanism leading to cell death may involve glutamate neuro/excitotoxicity. Mice fed cycad seed flour containing the isolated sterol glucosides show behavioral and neuropathological outcomes, including increased TdT-mediated biotin-dUTP nick-end labelling (TUNEL) positivity in various CNS regions. Astrocytes in culture showed increased caspase-3 labeling after exposure to sterol glucosides. The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders.
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U-K. Craig<affiliation><inist:fA14 i1="07"><s1>Lytico and Bodig Research Project, University of Guam</s1><s2>Mangilao</s2><s3>GUM</s3><sZ>13 aut.</sZ></inist:fA14><wicri:noCountry>GUM</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Isolation of various forms of sterol β-d-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex</title><author><name sortKey="Khabazian, I" sort="Khabazian, I" uniqKey="Khabazian I" first="I." last="Khabazian">I. Khabazian</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Bains, J S" sort="Bains, J S" uniqKey="Bains J" first="J. S." last="Bains">J. S. Bains</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Williams, D E" sort="Williams, D E" uniqKey="Williams D" first="D. E." last="Williams">D. E. Williams</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Chemistry and Earth and Ocean Sciences, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, J" sort="Cheung, J" uniqKey="Cheung J" first="J." last="Cheung">J. Cheung</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, J M B" sort="Wilson, J M B" uniqKey="Wilson J" first="J. M. B." last="Wilson">J. M. B. Wilson</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Program, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Pasqualotto, B A" sort="Pasqualotto, B A" uniqKey="Pasqualotto B" first="B. A." last="Pasqualotto">B. A. Pasqualotto</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Physiology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Pelech, S L" sort="Pelech, S L" uniqKey="Pelech S" first="S. L." last="Pelech">S. L. Pelech</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Kinexus Bioinformatics Corporation</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kinexus Bioinformatics Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Andersen, R J" sort="Andersen, R J" uniqKey="Andersen R" first="R. J." last="Andersen">R. J. Andersen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Y T" sort="Wang, Y T" uniqKey="Wang Y" first="Y.-T." last="Wang">Y.-T. Wang</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Liu, L" sort="Liu, L" uniqKey="Liu L" first="L." last="Liu">L. Liu</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Nagai, A" sort="Nagai, A" uniqKey="Nagai A" first="A." last="Nagai">A. Nagai</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Kim, S U" sort="Kim, S U" uniqKey="Kim S" first="S. U." last="Kim">S. U. Kim</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Craig, U K" sort="Craig, U K" uniqKey="Craig U" first="U-K." last="Craig">U-K. Craig</name><affiliation><inist:fA14 i1="07"><s1>Lytico and Bodig Research Project, University of Guam</s1><s2>Mangilao</s2><s3>GUM</s3><sZ>13 aut.</sZ></inist:fA14><wicri:noCountry>GUM</wicri:noCountry></affiliation></author><author><name sortKey="Shaw, C A" sort="Shaw, C A" uniqKey="Shaw C" first="C. A." last="Shaw">C. A. Shaw</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Program, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Experimental Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">03-0036792</idno><date when="2002">2002</date><idno type="stanalyst">PASCAL 03-0036792 INIST</idno><idno type="RBID">Pascal:03-0036792</idno><idno type="wicri:Area/PascalFrancis/Corpus">000B46</idno><idno type="wicri:Area/PascalFrancis/Curation">000177</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000A11</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000A11</idno><idno type="wicri:doubleKey">0022-3042:2002:Khabazian I:isolation:of:various</idno><idno type="wicri:Area/Main/Merge">003520</idno><idno type="wicri:Area/Main/Curation">003074</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Isolation of various forms of sterol β-d-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex</title><author><name sortKey="Khabazian, I" sort="Khabazian, I" uniqKey="Khabazian I" first="I." last="Khabazian">I. Khabazian</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Bains, J S" sort="Bains, J S" uniqKey="Bains J" first="J. S." last="Bains">J. S. Bains</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Williams, D E" sort="Williams, D E" uniqKey="Williams D" first="D. E." last="Williams">D. E. Williams</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Chemistry and Earth and Ocean Sciences, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, J" sort="Cheung, J" uniqKey="Cheung J" first="J." last="Cheung">J. Cheung</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Wilson, J M B" sort="Wilson, J M B" uniqKey="Wilson J" first="J. M. B." last="Wilson">J. M. B. Wilson</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Program, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Pasqualotto, B A" sort="Pasqualotto, B A" uniqKey="Pasqualotto B" first="B. A." last="Pasqualotto">B. A. Pasqualotto</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Physiology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Pelech, S L" sort="Pelech, S L" uniqKey="Pelech S" first="S. L." last="Pelech">S. L. Pelech</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Kinexus Bioinformatics Corporation</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kinexus Bioinformatics Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Andersen, R J" sort="Andersen, R J" uniqKey="Andersen R" first="R. J." last="Andersen">R. J. Andersen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Y T" sort="Wang, Y T" uniqKey="Wang Y" first="Y.-T." last="Wang">Y.-T. Wang</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Liu, L" sort="Liu, L" uniqKey="Liu L" first="L." last="Liu">L. Liu</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Nagai, A" sort="Nagai, A" uniqKey="Nagai A" first="A." last="Nagai">A. Nagai</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Kim, S U" sort="Kim, S U" uniqKey="Kim S" first="S. U." last="Kim">S. U. Kim</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Craig, U K" sort="Craig, U K" uniqKey="Craig U" first="U-K." last="Craig">U-K. Craig</name><affiliation><inist:fA14 i1="07"><s1>Lytico and Bodig Research Project, University of Guam</s1><s2>Mangilao</s2><s3>GUM</s3><sZ>13 aut.</sZ></inist:fA14><wicri:noCountry>GUM</wicri:noCountry></affiliation></author><author><name sortKey="Shaw, C A" sort="Shaw, C A" uniqKey="Shaw C" first="C. A." last="Shaw">C. A. Shaw</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Ophthalmology, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Program, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Experimental Medicine, University of British Columbia</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>14 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, British Columbia</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amyotrophic lateral sclerosis</term><term>Animal</term><term>Astrocyte</term><term>Cerebral cortex</term><term>Cycadales</term><term>Diet</term><term>Discharge pattern</term><term>Glucoside</term><term>Guam Parkinson dementia</term><term>In vitro</term><term>Mouse</term><term>NMDA receptor</term><term>Neuron</term><term>Neurotoxin</term><term>Plant origin</term><term>Toxicity</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Neurotoxine</term><term>Origine végétale</term><term>Cycadales</term><term>Toxicité</term><term>Récepteur NMDA</term><term>Glucoside</term><term>Astrocyte</term><term>Cortex cérébral</term><term>Sclérose latérale amyotrophique</term><term>Neurone</term><term>Mode décharge</term><term>Parkinson démence ile de Guam</term><term>Régime alimentaire</term><term>In vitro</term><term>Souris</term><term>Animal</term><term>Cycas circinalis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The factors responsible for ALS-parkinsonism dementia complex (ALS-PDC), the unique neurological disorder of Guam, remain unresolved, but identification of causal factors could lead to clues for related neurodegenerative disorders elsewhere. Earlier studies focused on the consumption and toxicity of the seed of Cycas circinalis, a traditional staple of the indigenous diet, but found no convincing evidence for toxin-linked neurodegeneration. We have reassessed the issue in a series of in vitro bioassays designed to isolate non-water soluble compounds from washed cycad flour and have identified three sterol β-D-glucosides as potential neurotoxins. These compounds give depolarizing field potentials in cortical slices, induce alterations in the activity of specific protein kinases, and cause release of glutamate. They are also highly toxic, leading to release of lactate dehydrogenase (LDH). The aglycone form, however, is non-toxic. NMDA receptor antagonists block the actions of the sterol glucosides, but do not compete for binding to the NMDA receptor. The most probable mechanism leading to cell death may involve glutamate neuro/excitotoxicity. Mice fed cycad seed flour containing the isolated sterol glucosides show behavioral and neuropathological outcomes, including increased TdT-mediated biotin-dUTP nick-end labelling (TUNEL) positivity in various CNS regions. Astrocytes in culture showed increased caspase-3 labeling after exposure to sterol glucosides. The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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