Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases

Proceedings of the National Academy of Sciences of the United States of America
Ruth A BodnerAleksey Kazantsev

Abstract

Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington's disease and alpha-synuclein in Parkinson's disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington's disease and Parkinson's disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces alpha-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington's and Parkinson's diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding.

References

Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·L WhitesellL M Neckers
Jun 8, 2001·Annual Review of Biochemistry·J Frydman
Mar 28, 2002·Physiological Reviews·Michael H Glickman, Aaron Ciechanover
Oct 11, 2002·Human Molecular Genetics·Lisette G G C VerhoefNico P Dantuma
Nov 8, 2002·Journal of Neurochemistry·Pamela J McLeanBradley T Hyman
Mar 26, 2003·Human Molecular Genetics·J Paul TaylorKenneth H Fischbeck
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Barbara L ApostolLeslie Michels Thompson
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Mar 27, 2004·The Journal of Biological Chemistry·Jochen KluckenPamela J McLean
Oct 8, 2004·The EMBO Journal·Carina I HolmbergRichard I Morimoto
Nov 27, 2004·Trends in Cell Biology·Christopher A Ross, Cecile M Pickart

❮ Previous
Next ❯

Citations

Mar 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gregor P Lotz, Justin Legleiter
Jun 2, 2010·Acta Neuropathologica·Sarah L Hands, Andreas Wyttenbach
Jun 30, 2012·Acta Neuropathologica·Darius Ebrahimi-FakhariPamela J McLean
Apr 30, 2008·Histochemistry and Cell Biology·P StrnadH Denk
Jun 25, 2013·Molecules and Cells·Tiffany W Todd, Janghoo Lim
Jan 24, 2009·Apoptosis : an International Journal on Programmed Cell Death·Oren A LevyLloyd A Greene
Feb 20, 2013·Journal of Molecular Neuroscience : MN·Anna Rocchi, Maria Pennuto
May 29, 2013·Pharmacology & Therapeutics·Ian F Harrison, David T Dexter
Jan 24, 2007·Lancet·Francis O Walker
Jun 29, 2007·Expert Reviews in Molecular Medicine·Jean-Christophe Rochet
Oct 12, 2011·Bioconjugate Chemistry·Yuka Matsushita-IshiodoriTakashi Ohtsuki
Jan 3, 2007·Biochemistry·Ronald WetzelAngela D Williams
Nov 11, 2011·Cell Death & Disease·D BanoP Nicotera
Aug 27, 2013·Nature Genetics·Robert P MasonFlaviano Giorgini
Mar 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Terrell E BrothertonJonathan D Glass
Aug 1, 2006·Photomedicine and Laser Surgery
Sep 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Karin M DanzerPamela J McLean
Jul 13, 2011·Cold Spring Harbor Perspectives in Biology·Bryan ChenJudith Frydman
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Steven Finkbeiner
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Leonidas Stefanis
Jun 29, 2010·FEMS Yeast Research·Sandra Tenreiro, Tiago Fleming Outeiro
Jun 26, 2007·Science·Tiago Fleming OuteiroAleksey G Kazantsev
Mar 10, 2009·Biochemistry. Biokhimii︠a︡·N BocharovaF Severin
Jan 12, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ray TruantAnjee Burtnik
Jun 22, 2012·International Journal of Alzheimer's Disease·Natalia Crespo-BielFred Van Leuven
Nov 17, 2007·BMC Bioinformatics·Koichi AbeKazunori Ikebukuro
Aug 28, 2012·Molecular Neurodegeneration·Karin M DanzerPamela J McLean
May 12, 2012·PLoS Computational Biology·Mahmoud MoradiCeleste Sagui
Jun 12, 2009·PloS One·Casey CookLeonard Petrucelli
Jul 22, 2011·International Journal of Environmental Research and Public Health·Stephen C Bondy
Nov 28, 2013·International Journal of Cell Biology·Sybille Krauss, Ina Vorberg
Aug 23, 2012·Journal of Biomedicine & Biotechnology·Clara PereiraLucília Saraiva
Sep 28, 2006·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Ray TruantRandy Singh Atwal
Sep 8, 2010·The Journal of Cell Biology·Peter M Douglas, Andrew Dillin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.