β‐Cyclodextrin interacts with the Alzheimer amyloid β‐A4 peptide

Camilleri, Patrick; Haskins, N. J.; Hewlett, David R.

doi:10.1016/0014-5793(94)80467-2

Cited by 113 publications

(110 citation statements)

References 11 publications

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“…Aksenov et al (1996a) reported that glutamine synthetase enhanced /3A neurotoxicity, while preventing fibril formation. Several treatments have been proposed to reduce /3A toxicity by an antiamyloidogenic mechanism that prevents the self-aggregation of /3A (Camilleri et al, 1994;Tomiyama et al, 1994;Pollack et al, 1996). However, the neuroprotective activity of two of these, rifampicin and sulfated compounds, was independent of their antiamyloidogenic activity.…”

Section: Discussionmentioning

confidence: 99%

Amidation of β‐Amyloid Peptide Strongly Reduced the Amyloidogenic Activity Without Alteration of the Neurotoxicity

Forloni

Lucca

Angeretti

et al. 1997

Journal of Neurochemistry

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/3-Amyloid accumulates in cerebral deposits in Alzheimer's disease, so to test the correlation between the neurotoxic and fibrillogenic capacity of /3-amyloid, we synthesized a peptide homologous to fragment 25-35 of /3-amyloid (/325-35) and amidated at the C-terminus (/325-35-NH 2). As the amidation strongly reduced the amyloidogenic capacity of /325-35, we compared its neurotoxic activity in the amidated (/325-35-NH2) and nonamidated forms. The viability of primary cultures from fetal rat hippocampus was reduced in a dose-related manner (10-100~sM)similarly by /325-35 and /325-35-NH2, whereas a scrambled peptide, amidated or nonamidated, did not alter the neuronal viability. The neurotoxic activity of /325-35-NH2 is mediated by apoptosis as demonstrated by morphological and biochemical investigations. Electron microscopy examination of culture media with /325-35 or /325-35-NH2 incubated with neuronal cells for 7 days confirmed the high level of fibrillogenic activity of /325-35 and the almost total absence of fibrils in the solution with /325-35-NH2. Furthermore, staining with thioflavine S was used to identify amyloid fibrils, and only the cultures exposed to /325-35 exhibited intense staining associated with neuronal membranes. These data indicate that the neurotoxic activity of the /3-amyloid fragment is independent of the aggregated state of the peptide.

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Section: Discussionmentioning

confidence: 99%

Amidation of β‐Amyloid Peptide Strongly Reduced the Amyloidogenic Activity Without Alteration of the Neurotoxicity

Forloni

Lucca

Angeretti

et al. 1997

Journal of Neurochemistry

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“…Additionally, β-CDs have been reported to be able to directly bind Aβ [69][70][71], and substantially decrease its neurotoxic effect in vitro. Another β-CD derivative, the per-6-alkylamino-β-CD, has been shown to interfere with the oligomerization process of Aβ 1-42 responsible in part for Aβ neurotoxicity [79].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE ® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer's, Parkinson's and Huntington's diseases are currently on-going.

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“…These characteristics include intracellular and extracellular aggregates of proteinaceous fibrils resulting from irregular protein-protein interactions (65). In a search for a new antiprion compound, ␤-cyclodextrin (␤-CD), which reduces the toxic effects of an AD-associated protein (␤-amyloid [A␤] [amino acids 1 to 40]) in cell culture (10), was tested here. The formation of ␤-sheet fibrils is a critical event in AD, and ␤-CD, by attenuating fibrillization of the toxic peptide, appears to inhibit the toxic effects of A␤ (10).…”

Section: Prpmentioning

confidence: 99%

“…In a search for a new antiprion compound, ␤-cyclodextrin (␤-CD), which reduces the toxic effects of an AD-associated protein (␤-amyloid [A␤] [amino acids 1 to 40]) in cell culture (10), was tested here. The formation of ␤-sheet fibrils is a critical event in AD, and ␤-CD, by attenuating fibrillization of the toxic peptide, appears to inhibit the toxic effects of A␤ (10). The CDs are macrocyclic, nonreducing maltooligosaccharides made from ␣-1,4-linked glucose units (58).…”

Section: Prpmentioning

confidence: 99%

Cyclodextrins Inhibit Replication of Scrapie Prion Protein in Cell Culture

Prior

Lehmann

et al. 2007

J Virol

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Prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal hostencoded protein, PrP C , to an abnormal, disease-causing form, PrP Sc . This paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein PrP Sc to undetectable levels in scrapieinfected neuroblastoma cells. Beta-cyclodextrin removed PrP Sc from the cells at a concentration of 500 M following 2 weeks of treatment. Structure activity studies revealed that antiprion activity was dependent on the size of the cyclodextrin. The half-maximal inhibitory concentration (IC 50 ) for beta-cyclodextrin was 75 M, whereas ␣-cyclodextrin, which possessed less antiprion activity, had an IC 50 of 750 M. This report presents cyclodextrins as a new class of antiprion compound. For decades, the pharmaceutical industry has successfully used cyclodextrins for their complex-forming ability; this ability is due to the structural orientation of the glucopyranose units, which generate a hydrophobic cavity that can facilitate the encapsulation of hydrophobic moieties. Consequently, cyclodextrins could be ideal candidates for the treatment of prion diseases.

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β‐Cyclodextrin interacts with the Alzheimer amyloid β‐A4 peptide

Cited by 113 publications

References 11 publications

Amidation of β‐Amyloid Peptide Strongly Reduced the Amyloidogenic Activity Without Alteration of the Neurotoxicity

Amidation of β‐Amyloid Peptide Strongly Reduced the Amyloidogenic Activity Without Alteration of the Neurotoxicity

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

Cyclodextrins Inhibit Replication of Scrapie Prion Protein in Cell Culture

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