Converse modulation of toxic alpha-synuclein oligomers in living cells by N'-benzylidene-benzohydrazide derivates and ferric iron.

Biochemical and Biophysical Research Communications
Andreas HillmerArmin Giese

Abstract

Intracellular alpha-synuclein (alpha-syn) aggregates are the pathological hallmark in several neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Recent evidence suggests that small oligomeric aggregates rather than large amyloid fibrils represent the main toxic particle species in these diseases. We recently characterized iron-dependent toxic alpha-syn oligomer species by confocal single molecule fluorescence techniques and used this aggregation model to identify several N'-benzylidene-benzohydrazide (NBB) derivatives inhibiting oligomer formation in vitro. In our current work, we used the bioluminescent protein-fragment complementation assay (BPCA) to directly analyze the formation of toxic alpha-syn oligomers in cell culture and to investigate the effect of iron and potential drug-like compounds in living cells. Similar to our previous findings in vitro, we found a converse modulation of toxic alpha-syn oligomers by NBB derivates and ferric iron, which was characterized by an increase in aggregate formation by iron and an inhibitory effect of certain NBB compounds. Inhibition of alpha-syn oligomer formation by the NBB compound 293G02 was paralleled by a reduction i...Continue Reading

References

Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·E H KooJ W Kelly
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·P KaskK Gall
Apr 4, 2000·Nature·M B Feany, W W Bender
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·J BieschkeH Kretzschmar
Dec 25, 2002·Neurobiology of Aging·Heiko BraakEva Braak
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Dec 16, 2006·The Journal of Biological Chemistry·Niclas W SchifferBettina Schmid
Jun 30, 2007·Nature Reviews. Drug Discovery·Stephen W MichnickEduard Stefan
Aug 30, 2008·The Journal of Biological Chemistry·Charles G Glabe
Jul 28, 2009·Expert Reviews in Molecular Medicine·Thomas Gasser

❮ Previous
Next ❯

Citations

Oct 5, 2011·The Journal of Biological Chemistry·Marino ConvertinoAmedeo Caflisch
Nov 26, 2011·Antioxidants & Redox Signaling·D Allan ButterfieldRukhsana Sultana
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong Liu, Zhonglu You
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong Liu, Zhonglu You
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong Liu, Zhonglu You
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong Liu, Xiaoling Wang
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong Liu, Xiaoling Wang
Jul 15, 2011·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong LiuXiao-Fang Li
Aug 13, 2011·Acta Crystallographica. Section E, Structure Reports Online·Shi-Yong LiuXiao-Ling Wang
Nov 18, 2011·Acta Crystallographica. Section E, Structure Reports Online·Hai-Chang GuoXiao-Ling Wang
Dec 15, 2010·Molecular Neurodegeneration·Peizhou JiangShu-Hui C Yen
Feb 5, 2016·Molecular Neurobiology·Junjun ZhaoJianliang Zhang
Dec 12, 2012·Neurochemistry International·Claudia FunkeDouglas B Kell
Aug 27, 2011·Metallomics : Integrated Biometal Science·Leonid Breydo, Vladimir N Uversky
Apr 25, 2013·Physical Chemistry Chemical Physics : PCCP·Armin HoffmannMichael T Woodside
Nov 7, 2019·Oxidative Medicine and Cellular Longevity·Dinendra L Abeyawardhane, Heather R Lucas
Oct 26, 2011·Biochimica Et Biophysica Acta·Leonid BreydoVladimir N Uversky

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.

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.

Bovine Spongiform Encephalopathy (MDS)

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alpha-Synuclein Aggregation

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.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.