Short A{beta} peptides attenuate A{beta}42 toxicity in vivo

Publication Date:
2018-01-03
Publisher:
Rockefeller University Press
Print ISSN:
0022-1007
Electronic ISSN:
1540-9538
Topics:
Medicine
Keywords:
Neuroscience
Published by:
http://www.rupress.org/
_version_ 1836398729017425921
autor Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
beschreibung Processing of amyloid-β (Aβ) precursor protein (APP) by -secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). -Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
citation_standardnr 6127774
datenlieferant ipn_articles
feed_id 96
feed_publisher Rockefeller University Press
feed_publisher_url http://www.rupress.org/
insertion_date 2018-01-03
journaleissn 1540-9538
journalissn 0022-1007
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Rockefeller University Press
quelle Journal of Experimental Medicine
relation http://jem.rupress.org/cgi/content/short/215/1/283?rss=1
schlagwort Neuroscience
search_space articles
shingle_author_1 Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
shingle_author_2 Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
shingle_author_3 Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
shingle_author_4 Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
shingle_catch_all_1 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
Neuroscience
Processing of amyloid-β (Aβ) precursor protein (APP) by -secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). -Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_2 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
Neuroscience
Processing of amyloid-β (Aβ) precursor protein (APP) by -secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). -Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_3 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
Neuroscience
Processing of amyloid-β (Aβ) precursor protein (APP) by -secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). -Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_4 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
Neuroscience
Processing of amyloid-β (Aβ) precursor protein (APP) by -secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). -Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
Moore, B. D., Martin, J., de Mena, L., Sanchez, J., Cruz, P. E., Ceballos-Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., Kurian, J. J., McKenna, R., Koo, E. H., Borchelt, D. R., Janus, C., Rincon-Limas, D., Fernandez-Funez, P., Golde, T. E.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_title_1 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
shingle_title_2 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
shingle_title_3 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
shingle_title_4 Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
timestamp 2025-06-30T23:31:42.268Z
titel Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
titel_suche Short A{beta} peptides attenuate A{beta}42 toxicity in vivo
topic WW-YZ
uid ipn_articles_6127774