Amyloid-beta peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor.

Joslin, Gregg; Krause, James E.; Hershey, Andrew D.; Adams, Steve; Fallon, Robert J.; Perlmutter, David H.

doi:10.1016/s0021-9258(18)54721-9

Cited by 99 publications

(3 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The evidence presented here points to an additional possibility, namely, that the release of an HCHWA-D 3/A4 fragment by whatever proteolytic pathway results in a polypeptide species that has a greater tendency to assemble into stable amyloid fibrils. This aggregated 3-conformation may be necessary for interaction with a receptor, for example, the serpin-enzyme complex (SEC) receptor, which has recently been shown to bind 3/ A4 fragments (Joslin et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Fibril formation by primate, rodent, and Dutch-hemorrhagic analogs of Alzheimer amyloid .beta.-protein

Fraser¹,

et al. 1992

View full text Add to dashboard Cite

Deposition of extraneuronal fibrils that assemble from the 39-43 residue beta/A4 amyloid protein is one of the earliest histopathological features of Alzheimer's disease. We have used negative-stain electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, and fiber X-ray diffraction to examine the structure and properties of synthetic peptides corresponding to residues 1-40 of the beta/A4 protein of primate [Pm(1-40); human and monkey], rodent [Ro(1-40); with Arg5-->Gly, Tyr10-->Phe, and His13-->Arg], and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) [Du(1-40); with Glu22-->Gln]. As controls, we examined a reverse primate sequence [Pm*(40-1)] and an extensively substituted primate peptide [C(1-40); with Glu3-->Arg, Arg5-->Glu, Asp7-->Val, His13-->Lys, Lys16-->His, Val18-->Asp, Phe19-->Ser, Phe20-->Tyr, Ser26-->Pro, Ala30-->Val, Ile31-->Ala, Met35-->norLeu, Gly38-->Ile, Val39-->Ala, and Val40-->Gly]. The assembly of these peptides was studied to understand the relationship between species-dependent amyloid formation and beta/A4 sequence and the effect of a naturally occurring point mutation of fibrillogenesis. The three N-terminal amino acid differences between Pm(1-40) and Ro(1-40) had virtually no effect on the morphology or organization of the fibrils formed by these peptides, indicating that the lack of amyloid deposits in rodent brain is not due directly to specific changes in its beta/A4 sequence. beta-Sheet and fibril formation, judged by FT-IR, was maximal within the pH range 5-8 for Pm(1-40), pH 5-10.5 for Du(1-40), and pH 2.5-8 for Ro(1-40).(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussionmentioning

confidence: 99%

Fibril formation by primate, rodent, and Dutch-hemorrhagic analogs of Alzheimer amyloid .beta.-protein

Fraser¹,

et al. 1992

View full text Add to dashboard Cite

show abstract

“…The exact mechanism of Aβ neurotoxicity is debated; for review, see Iverson et al (3) or Mattson (4). Several groups have proposed that Aβ associates specifically with cells via membrane-bound receptors (5)(6)(7)(8)(9). However, the discoveries that both D-and L-enantiomers of Aβ produce fibrillar aggregates with identical structural and cytotoxic properties (10) and that fibrils consisting of either amylin or Aβ, with similar structure but distinct sequence, induce similar changes in gene expression (11) suggest that the interaction between Aβ and neurons may not be mediated via specific Aβreceptor association.…”

mentioning

confidence: 99%

Correlation of β-Amyloid Aggregate Size and Hydrophobicity with Decreased Bilayer Fluidity of Model Membranes

et al. 2000

View full text Add to dashboard Cite

beta-amyloid peptide (Abeta) is the primary constituent of senile plaques, a defining feature of Alzheimer's disease. Aggregated Abeta is toxic to neurons, but the mechanism of toxicity remains unproven. One proposal is that Abeta toxicity results from relatively nonspecific Abeta-membrane interactions. We hypothesized that Abeta perturbs membrane structure as a function of the aggregation state of Abeta. Toward exploring this hypothesis, Abeta aggregate size and hydrophobicity were characterized using dynamic and static light scattering and 1,1-bis(4-anilino)naphthalene-5,5-disulfonic acid (bis-ANS) fluorescence. The effect of Abeta aggregation state on the membrane fluidity of unilamellar liposomes was assessed by monitoring the anisotropy of the membrane-embedded fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene (DPH). Unaggregated Abeta at pH 7 did not bind bis-ANS and had little to no effect on membrane fluidity. More significantly, Abeta aggregated at pH 6 or 7 decreased membrane fluidity in a time- and dose-dependent manner. Aggregation rate and surface hydrophobicity were considerably greater for Abeta aggregated at pH 6 than at neutral pH and were strongly correlated with the extent of decrease in membrane fluidity. Prolonged (7 days) Abeta aggregation resulted in a return to near-baseline levels in both bis-ANS fluorescence and DPH anisotropy at pH 7 but not at pH 6. The addition of gangliosides to the liposomes significantly increased the DPH anisotropy response. Hence, self-association of Abeta monomers into aggregates exposes hydrophobic sites and induces a decrease in membrane fluidity. Abeta aggregate-induced changes in membrane physical properties may have deleterious consequences on cellular functioning.

show abstract

“…Evidence in favor of βAP binding to several cell surface receptors has been presented. The serpin−enzyme complex receptor recognizes soluble, nontoxic β-amyloid peptide but not aggregated cytotoxic β-amyloid peptide ( , ). It does not mediate the cytotoxic effect of aggregated βAP but could play a protective role by mediating clearance and catabolism of monomeric, soluble βAP.…”

mentioning

confidence: 99%

Interaction of Alzheimer β-Amyloid Peptide(1−40) with Lipid Membranes

1997

View full text Add to dashboard Cite

The beta-amyloid peptide beta AP(1-40), a 40-amino acid residues peptide, is one of the major components of Alzheimer's amyloid deposits. beta AP(1-40) exhibits only a limited solubility in aqueous solution and undergoes a concentration-dependent, cooperative random coil reversible beta-structure transition for Cpep > 10 microM [Terzi, E., Hölzemann, G., and Seelig, J. (1995) J. Mol. Biol. 252, 633-642]. In the presence of acidic lipid, the equilibrium is shifted further toward beta-structured aggregates. We have now characterized the lipid-peptide interaction using circular dichroism (CD) spectroscopy, lipid monolayers, and deuterium and phosphorus-31 solid-state nuclear magnetic resonance (NMR). CD spectroscopy revealed a distinct interaction between beta AP(1-40) and negatively charged unilamellar vesicles. In addition to the random coil reversible beta-structured aggregate equilibrium at low lipid-to-peptide (L/P) ratios, a beta-structure -->alpha-helix transition was observed at L/P > 55. beta AP(1-40) was found to insert into acidic monolayers provided the lateral pressure was low (20 mN/m). The extent of incorporation increased distinctly with the content of acidic lipid in the monolayer. However, at a lipid packing density equivalent to that of a bilayer (lateral pressure> or = 32 mN/m), no insertion of beta AP(1-40) was observed. The lipid molecular structure in the presence of beta AP(1-40) was studied with NMR. Phosphatidylcholine (PC) was selectively deuterated at the choline headgroup and at the cis-double bond of the oleic acyl chain and mixed with phosphatidylglycerol (PG). Phosphorus-31 NMR showed that the lipid phase retained the bilayer structure at all lipid-to-protein ratios. Deuterium NMR revealed no change in the headgroup conformation of the choline moiety or in the flexibility and ordering of the hydrocarbon chains upon the addition of beta AP-(1-40). It can be concluded that beta AP(1-40) binds electrostatically to the outer envelope of the polar headgroup region without penetrating between the polar groups. The data suggest a new mechanism of helix formation induced by the proper alignment of five positive charges of beta AP(1-40) on the negatively charged membrane template.

show abstract

Amyloid-beta peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor.

Cited by 99 publications

References 32 publications

Fibril formation by primate, rodent, and Dutch-hemorrhagic analogs of Alzheimer amyloid .beta.-protein

Fibril formation by primate, rodent, and Dutch-hemorrhagic analogs of Alzheimer amyloid .beta.-protein

Correlation of β-Amyloid Aggregate Size and Hydrophobicity with Decreased Bilayer Fluidity of Model Membranes

Interaction of Alzheimer β-Amyloid Peptide(1−40) with Lipid Membranes

Contact Info

Product

Resources

About