Abstract
Soluble and toxic oligomers of amyloid β (Aβ) protein have been identified as the true neurotoxic species involved in Alzheimer's disease and considering them as targets to inhibit Aβ aggregation might have a therapeutic value. We previously set up a CE method that enables the separation and quantification of transient oligomers of Aβ protein-containing 42 amino acids (Aβ1-42) along the pathway leading to fibrils and we now demonstrate how this method can be successfully applied to examine the in vitro inhibitory effects of small molecules on Aβ oligomerization. To this end, we investigated mitoxantrone and pixantrone, two well-known anticancer drugs, as well as suramin and a suramin-like compound. By using CE, it is here shown how mitoxantrone and pixantrone either reduce or block Aβ1-42 oligomerization, while Thioflavin T spectrofluorimetric assay and transmission electron microscopy demonstrate how these two compounds also display antifibrillogenic activity. Interestingly, in vitro cell viability experiments indicated that pixantrone significantly reduces Aβ1-42 neurotoxicity.
| Original language | English |
|---|---|
| Pages (from-to) | 1418-1429 |
| Number of pages | 12 |
| Journal | Electrophoresis |
| Volume | 30 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2009 |
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Keywords
- Alzheimer's disease
- Amyloid β
- CE
- Mitoxantrone
- Pixantrone
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
Cite this
CE can identify small molecules that selectively target soluble oligomers of amyloid β protein and display antifibrillogenic activity. / Colombo, Raffaella; Carotti, Angelo; Catto, Marco; Racchi, Marco; Lanni, Cristina; Verga, Laura; Caccialanza, Gabriele; De Lorenzi, Ersilia.
In: Electrophoresis, Vol. 30, No. 8, 2009, p. 1418-1429.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CE can identify small molecules that selectively target soluble oligomers of amyloid β protein and display antifibrillogenic activity
AU - Colombo, Raffaella
AU - Carotti, Angelo
AU - Catto, Marco
AU - Racchi, Marco
AU - Lanni, Cristina
AU - Verga, Laura
AU - Caccialanza, Gabriele
AU - De Lorenzi, Ersilia
PY - 2009
Y1 - 2009
N2 - Soluble and toxic oligomers of amyloid β (Aβ) protein have been identified as the true neurotoxic species involved in Alzheimer's disease and considering them as targets to inhibit Aβ aggregation might have a therapeutic value. We previously set up a CE method that enables the separation and quantification of transient oligomers of Aβ protein-containing 42 amino acids (Aβ1-42) along the pathway leading to fibrils and we now demonstrate how this method can be successfully applied to examine the in vitro inhibitory effects of small molecules on Aβ oligomerization. To this end, we investigated mitoxantrone and pixantrone, two well-known anticancer drugs, as well as suramin and a suramin-like compound. By using CE, it is here shown how mitoxantrone and pixantrone either reduce or block Aβ1-42 oligomerization, while Thioflavin T spectrofluorimetric assay and transmission electron microscopy demonstrate how these two compounds also display antifibrillogenic activity. Interestingly, in vitro cell viability experiments indicated that pixantrone significantly reduces Aβ1-42 neurotoxicity.
AB - Soluble and toxic oligomers of amyloid β (Aβ) protein have been identified as the true neurotoxic species involved in Alzheimer's disease and considering them as targets to inhibit Aβ aggregation might have a therapeutic value. We previously set up a CE method that enables the separation and quantification of transient oligomers of Aβ protein-containing 42 amino acids (Aβ1-42) along the pathway leading to fibrils and we now demonstrate how this method can be successfully applied to examine the in vitro inhibitory effects of small molecules on Aβ oligomerization. To this end, we investigated mitoxantrone and pixantrone, two well-known anticancer drugs, as well as suramin and a suramin-like compound. By using CE, it is here shown how mitoxantrone and pixantrone either reduce or block Aβ1-42 oligomerization, while Thioflavin T spectrofluorimetric assay and transmission electron microscopy demonstrate how these two compounds also display antifibrillogenic activity. Interestingly, in vitro cell viability experiments indicated that pixantrone significantly reduces Aβ1-42 neurotoxicity.
KW - Alzheimer's disease
KW - Amyloid β
KW - CE
KW - Mitoxantrone
KW - Pixantrone
UR - http://www.scopus.com/inward/record.url?scp=65949093940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65949093940&partnerID=8YFLogxK
U2 - 10.1002/elps.200800377
DO - 10.1002/elps.200800377
M3 - Article
C2 - 19306269
AN - SCOPUS:65949093940
VL - 30
SP - 1418
EP - 1429
JO - Electrophoresis
JF - Electrophoresis
SN - 0173-0835
IS - 8
ER -