Dense Shell Glycodendrimers as Potential Nontoxic Anti-amyloidogenic Agents in Alzheimer’s Disease. Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity
Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low in...
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| Veröffentlicht in: | Biomacromolecules 2011-11, Vol.12 (11), p.3903-3909 |
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| creator | Klementieva, Oxana Benseny-Cases, Núria Gella, Alejandro Appelhans, Dietmar Voit, Brigitte Cladera, Josep |
| description | Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low intrinsic toxicity. In the present paper we show that fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation glycodendrimers have the capacity to interfere with Alzheimer’s amyloid peptide Aβ(1–40) fibrilization. The interaction is generation dependent: PPI-G5-Mal blocks amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer–peptide ratios and amorphous aggregates at high ratios. Both PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells. PPI-G4-Mal reduces amyloid toxicity by clumping fibrils together, whereas amorphous aggregates are toxic to PC12 cells. The results show that glycodendrimers are promising nontoxic agents in the search for anti-amyloidogenic compounds. Fibril clumping may be an anti-amyloid toxicity strategy. |
| doi_str_mv | 10.1021/bm2008636 |
| format | Article |
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Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity</title><source>ACS Publications</source><source>MEDLINE</source><creator>Klementieva, Oxana ; Benseny-Cases, Núria ; Gella, Alejandro ; Appelhans, Dietmar ; Voit, Brigitte ; Cladera, Josep</creator><creatorcontrib>Klementieva, Oxana ; Benseny-Cases, Núria ; Gella, Alejandro ; Appelhans, Dietmar ; Voit, Brigitte ; Cladera, Josep</creatorcontrib><description>Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low intrinsic toxicity. In the present paper we show that fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation glycodendrimers have the capacity to interfere with Alzheimer’s amyloid peptide Aβ(1–40) fibrilization. The interaction is generation dependent: PPI-G5-Mal blocks amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer–peptide ratios and amorphous aggregates at high ratios. Both PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells. PPI-G4-Mal reduces amyloid toxicity by clumping fibrils together, whereas amorphous aggregates are toxic to PC12 cells. The results show that glycodendrimers are promising nontoxic agents in the search for anti-amyloidogenic compounds. Fibril clumping may be an anti-amyloid toxicity strategy.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm2008636</identifier><identifier>PMID: 21936579</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Alzheimer Disease - drug therapy ; Amyloid - chemistry ; Amyloid - ultrastructure ; Amyloid beta-Peptides - chemistry ; Animals ; Applied sciences ; Biological and medical sciences ; Cell Line, Tumor ; Cell Survival ; Dendrimers - chemistry ; Dendrimers - pharmacology ; Exact sciences and technology ; Humans ; Kinetics ; Maltose - chemistry ; Maltose - pharmacology ; Medical sciences ; Neuropharmacology ; Organic polymers ; PC12 Cells ; Peptide Fragments - chemistry ; Pharmacology. Drug treatments ; Physicochemistry of polymers ; Polypropylenes - chemistry ; Polypropylenes - pharmacology ; Properties and characterization ; Protein Multimerization ; Protein Structure, Quaternary ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. 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Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low intrinsic toxicity. In the present paper we show that fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation glycodendrimers have the capacity to interfere with Alzheimer’s amyloid peptide Aβ(1–40) fibrilization. The interaction is generation dependent: PPI-G5-Mal blocks amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer–peptide ratios and amorphous aggregates at high ratios. Both PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells. PPI-G4-Mal reduces amyloid toxicity by clumping fibrils together, whereas amorphous aggregates are toxic to PC12 cells. The results show that glycodendrimers are promising nontoxic agents in the search for anti-amyloidogenic compounds. Fibril clumping may be an anti-amyloid toxicity strategy.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Amyloid - chemistry</subject><subject>Amyloid - ultrastructure</subject><subject>Amyloid beta-Peptides - chemistry</subject><subject>Animals</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival</subject><subject>Dendrimers - chemistry</subject><subject>Dendrimers - pharmacology</subject><subject>Exact sciences and technology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Maltose - chemistry</subject><subject>Maltose - pharmacology</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Organic polymers</subject><subject>PC12 Cells</subject><subject>Peptide Fragments - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemistry of polymers</subject><subject>Polypropylenes - chemistry</subject><subject>Polypropylenes - pharmacology</subject><subject>Properties and characterization</subject><subject>Protein Multimerization</subject><subject>Protein Structure, Quaternary</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Solution and gel properties</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1u1DAQxyMEoqVw4AWQL0j0kGLHH4mPq11akMqHRDlHjjPZTeXYiycrEU59B04cebU-CQ67bS-cZsb6zX_G88-yl4yeMVqwt81QUFoprh5lx0wWKheKFo__5TIvS10eZc8Qrymlmgv5NDsqmOZKlvo4-7MCj0C-bsA5cuEmG1rwbewHiEgMki9hBD_2xpFPwY_hR2_JItW5GSYX-jaswc9PKYxIek8W7ucG5u7bm99IVj2CQTgjiz1-e_NrdSefmtYR1mYEJB9D3G6CC-uJGN-S5bzM1TysH6fn2ZPOOIQXh3iSfTt_d7V8n19-vviwXFzmhpflmGtpBChdSVnajnbQKGslM42AqisaztuisU0lGUBhFKWqkkoKzXgDrDGdFvwke7PX3cbwfQc41kOPNm1iPIQd1umYguuy0jqhp3vUxoAYoau36UsmTjWj9exIfe9IYl8dZHfNAO09eWdBAl4fAIPWuC4ab3t84ESphBbVA2cs1tdhF326xn8G_gWJvqO2</recordid><startdate>20111114</startdate><enddate>20111114</enddate><creator>Klementieva, Oxana</creator><creator>Benseny-Cases, Núria</creator><creator>Gella, Alejandro</creator><creator>Appelhans, Dietmar</creator><creator>Voit, Brigitte</creator><creator>Cladera, Josep</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20111114</creationdate><title>Dense Shell Glycodendrimers as Potential Nontoxic Anti-amyloidogenic Agents in Alzheimer’s Disease. Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity</title><author>Klementieva, Oxana ; Benseny-Cases, Núria ; Gella, Alejandro ; Appelhans, Dietmar ; Voit, Brigitte ; Cladera, Josep</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a377t-95a4e698557cf0feb6cc51ab4e8f2b33d2bcb851ee2a600685654913be1baf943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Amyloid - chemistry</topic><topic>Amyloid - ultrastructure</topic><topic>Amyloid beta-Peptides - chemistry</topic><topic>Animals</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival</topic><topic>Dendrimers - chemistry</topic><topic>Dendrimers - pharmacology</topic><topic>Exact sciences and technology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Maltose - chemistry</topic><topic>Maltose - pharmacology</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Organic polymers</topic><topic>PC12 Cells</topic><topic>Peptide Fragments - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemistry of polymers</topic><topic>Polypropylenes - chemistry</topic><topic>Polypropylenes - pharmacology</topic><topic>Properties and characterization</topic><topic>Protein Multimerization</topic><topic>Protein Structure, Quaternary</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Solution and gel properties</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klementieva, Oxana</creatorcontrib><creatorcontrib>Benseny-Cases, Núria</creatorcontrib><creatorcontrib>Gella, Alejandro</creatorcontrib><creatorcontrib>Appelhans, Dietmar</creatorcontrib><creatorcontrib>Voit, Brigitte</creatorcontrib><creatorcontrib>Cladera, Josep</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klementieva, Oxana</au><au>Benseny-Cases, Núria</au><au>Gella, Alejandro</au><au>Appelhans, Dietmar</au><au>Voit, Brigitte</au><au>Cladera, Josep</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dense Shell Glycodendrimers as Potential Nontoxic Anti-amyloidogenic Agents in Alzheimer’s Disease. Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2011-11-14</date><risdate>2011</risdate><volume>12</volume><issue>11</issue><spage>3903</spage><epage>3909</epage><pages>3903-3909</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><abstract>Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low intrinsic toxicity. In the present paper we show that fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation glycodendrimers have the capacity to interfere with Alzheimer’s amyloid peptide Aβ(1–40) fibrilization. The interaction is generation dependent: PPI-G5-Mal blocks amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer–peptide ratios and amorphous aggregates at high ratios. Both PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells. PPI-G4-Mal reduces amyloid toxicity by clumping fibrils together, whereas amorphous aggregates are toxic to PC12 cells. The results show that glycodendrimers are promising nontoxic agents in the search for anti-amyloidogenic compounds. Fibril clumping may be an anti-amyloid toxicity strategy.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>21936579</pmid><doi>10.1021/bm2008636</doi><tpages>7</tpages></addata></record> |
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| subjects | Alzheimer Disease - drug therapy Amyloid - chemistry Amyloid - ultrastructure Amyloid beta-Peptides - chemistry Animals Applied sciences Biological and medical sciences Cell Line, Tumor Cell Survival Dendrimers - chemistry Dendrimers - pharmacology Exact sciences and technology Humans Kinetics Maltose - chemistry Maltose - pharmacology Medical sciences Neuropharmacology Organic polymers PC12 Cells Peptide Fragments - chemistry Pharmacology. Drug treatments Physicochemistry of polymers Polypropylenes - chemistry Polypropylenes - pharmacology Properties and characterization Protein Multimerization Protein Structure, Quaternary Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Solution and gel properties |
| title | Dense Shell Glycodendrimers as Potential Nontoxic Anti-amyloidogenic Agents in Alzheimer’s Disease. Amyloid–Dendrimer Aggregates Morphology and Cell Toxicity |
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