Modulatory Effects of pH, Cu+2 and Sheet Breakers on Aggregation of Amyloid Peptides

Beking, Kris; Hao, Xiaolei; Basak, Sarmistha; Basak, Ajoy

doi:10.2174/0929866053005845

Cited by 11 publications

(14 citation statements)

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“…Analogously, although MALDI-TOF and ESI/MS could be very useful to characterize a newly synthesized decapeptide with an amino acid sequence contained in the full-length Ab, CD, as well as AFM investigations, were necessary to study the influence of the environmental conditions (the presence of metal ions or sodium dodecyl sulfate (SDS)) on the secondary structure of the peptide to confirm a morphological change before and after copper treatment and/or SDS in the surface packing of the peptide shell (Murariu, Dragan, & Drochioiu, 2007). Similar results have also been obtained for the full-length Ab by coupling MS and CD, because it was found that Cu 2þ led to oxidative degradation or aggregation, depending on its concentration and time of incubation, whereas b-sheet breakers can reverse the selfaggregation process (Beking et al, 2005).…”

Section: B Other Analytical Approachessupporting

confidence: 64%

The use of mass spectrometry to study amyloid‐β peptides

Grasso

2010

Mass Spectrometry Reviews

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Amyloid-β peptide (Aβ) varies in size from 39 to 43 amino acids and arises from sequential β- and γ-secretase processing of the amyloid precursor protein. Whereas the non-pathological role for Aβ is yet to be established, there is no disputing that Aβ is now widely regarded as central to the development of Alzheimer's disease (AD). The so named "amyloid cascade hypothesis" states that disease progression is the result of an increased Aβ burden in affected areas of the brain. To elucidate the Aβ role in AD, many analytical approaches have been proposed as suitable tools to investigate not only the total Aβ load but also many other issues that are considered crucial for AD, such as: (i) the aggregation state in which Aβ is present; (ii) its interaction with other species or metals; (iii) its ability to induce oxidative stress; and (iv) its degradative pathways. This review provides an insight into the use of mass spectrometry (MS) in the field of Aβ investigation aimed to assess its role in AD. In particular, the different MS-based approaches applied in vitro and in vivo that can provide detailed information on the above-mentioned issues are reviewed. Moreover, the advantages offered by the MS methods over all the other techniques are highlighted, together with the recent developments and uses of combined analytical approaches to detect and characterize Aβ.

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Section: B Other Analytical Approachessupporting

confidence: 64%

The use of mass spectrometry to study amyloid‐β peptides

Grasso

2010

Mass Spectrometry Reviews

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“…The capability to cause membrane fusion and to promote lipid reorganization was already detected for the C-terminal domain of the amyloid peptide Aβ (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). 30 Our investigation extends this property to the more relevant natural form of Aβ.…”

Section: Discussionmentioning

confidence: 94%

“…In our previous work, we have applied neutron diffraction to stacked lipid multilayers to localize a selectively deuterated amino acid of the short Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Membrane perturbation and peptide insertion in the hydrophobic core were our main results.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there is evidence that Aβ and other amyloidogenic proteins can penetrate the membrane, leading to permeabilization and to pore formation. 9 In our previous investigations, we had applied neutron diffraction and selective deuteration to localize the short peptide Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), a toxic fragment of Aβ, into lipid bilayers of different surface charge and composition. [10][11][12] In the present study, the interaction of the most abundant Aβ in senile plaques, that is, Aβ , with unilamellar lipid vesicles (ULVs) is investigated by small-angle neutron scattering (SANS).…”

Section: Introductionmentioning

confidence: 99%

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Membrane Fusogenic Activity of the Alzheimer's Peptide Aβ(1–42) Demonstrated by Small-Angle Neutron Scattering

Dante¹,

Hauß

Brandt³

et al. 2008

Journal of Molecular Biology

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“…Of particular note, b-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid b peptide by blocking and/ or reversing the misfolding process. [58,59,61,62] Several inhibitors of Ab fibril formation have been reported, [11,[63][64][65][66][67][68][69][70][71] however, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric hindrance to prevent interactions between large peptide surfaces.…”

Section: Ab42 Self-aggregation Inhibition Studiesmentioning

confidence: 99%

Insight Into the Kinetic of Amyloid β (1–42) Peptide Self‐Aggregation: Elucidation of Inhibitors’ Mechanism of Action

et al. 2007

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The initial transition of amyloid beta (1-42) (Abeta42) soluble monomers/small oligomers from unordered/alpha-helix to a beta-sheet-rich conformation represents a suitable target to design new potent inhibitors and to obtain effective therapeutics for Alzheimer's disease. Under optimized conditions, this reliable and reproducible CD kinetic study showed a three-step sigmoid profile that was characterized by a lag phase (prevailing unordered/alpha-helix conformation), an exponential growth phase (increasing beta-sheet secondary structure) and a plateau phase (prevailing beta-sheet secondary structure). This kinetic analysis brought insight into the inhibitors' mechanism of action. In fact, an increase in the duration of the lag phase can be related to the formation of an inhibitor-Abeta complex, in which the non-amyloidogenic conformation is stabilized. When the exponential rate is affected exclusively, such as in the case of Congo red and tetracycline, then the inhibitor affinity might be higher for the pleated beta-sheet structure. Finally, by adding the inhibitor at the end of the exponential phase, the soluble protofibrils can be disrupted and the Abeta amyloidogenic structure can revert into monomers/small oligomers. Congo red and tetracycline preferentially bind to amyloid in the beta-sheet conformation because both decreased the slope of the exponential growth, even if to a different extent, whereas no effect was observed for tacrine and galantamine. Some very preliminary indications can be derived about the structural requirements for binding to nonamyloidogenic or beta-sheet amyloid secondary structure for the development of potent antiaggregating agents. On these premises, memoquin, a multifunctional molecule that was designed to become a drug candidate for the treatment of Alzheimer's disease, was investigated under the reported circular dichroism assay and its anti-amyloidogenic mechanism of action was elucidated.

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Modulatory Effects of pH, Cu+2 and Sheet Breakers on Aggregation of Amyloid Peptides

Cited by 11 publications

References 0 publications

The use of mass spectrometry to study amyloid‐β peptides

The use of mass spectrometry to study amyloid‐β peptides

Membrane Fusogenic Activity of the Alzheimer's Peptide Aβ(1–42) Demonstrated by Small-Angle Neutron Scattering

Insight Into the Kinetic of Amyloid β (1–42) Peptide Self‐Aggregation: Elucidation of Inhibitors’ Mechanism of Action

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