Dataset Information

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image A?42 to the Natural l-Enantiomer.

ABSTRACT: Racemates often have lower solubility than enantiopure compounds, and the mixing of enantiomers can enhance the aggregation propensity of peptides. Amyloid beta (A?) 42 is an aggregation-prone peptide that is believed to play a key role in Alzheimer's disease. Soluble A?42 aggregation intermediates (oligomers) have emerged as being particularly neurotoxic. We hypothesized that the addition of mirror-image d-A?42 should reduce the concentration of toxic oligomers formed from natural l-A?42. We synthesized l- and D-A?42 and found their equimolar mixing to lead to accelerated fibril formation. Confocal microscopy with fluorescently labeled analogues of the enantiomers showed their colocalization in racemic fibrils. Owing to the enhanced fibril formation propensity, racemic A?42 was less prone to form soluble oligomers. This resulted in the protection of cells from the toxicity of l-A?42 at concentrations up to 50??m. The mixing of A?42 enantiomers thus accelerates the formation of non-toxic fibrils.

SUBMITTER: Dutta S

PROVIDER: S-EPMC5623316 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image Aβ42 to the Natural l-Enantiomer.

Dutta Subrata S Foley Alejandro R AR Warner Christopher J A CJA Zhang Xiaolin X Rolandi Marco M Abrams Benjamin B Raskatov Jevgenij A JA

Angewandte Chemie (International ed. in English) 20170719 38

Racemates often have lower solubility than enantiopure compounds, and the mixing of enantiomers can enhance the aggregation propensity of peptides. Amyloid beta (Aβ) 42 is an aggregation-prone peptide that is believed to play a key role in Alzheimer's disease. Soluble Aβ42 aggregation intermediates (oligomers) have emerged as being particularly neurotoxic. We hypothesized that the addition of mirror-image d-Aβ42 should reduce the concentration of toxic oligomers formed from natural l-Aβ42. We sy ...[more]

PMID: 28682473

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Project description:BACKGROUND: Gnosis is a modality-specific ability to access semantic knowledge of an object or stimulus in the presence of normal perception. Failure of this is agnosia or disorder of recognition. It can be highly selective within a mode. self-images are different from others as none has seen one's own image except in reflection. Failure to recognize this image can be labeled as mirror image agnosia or Prosopagnosia for reflected self-image. Whereas mirror agnosia is a well-recognized situation where the person while looking at reflected images of other objects in the mirror he imagines that the objects are in fact inside the mirror and not outside. MATERIAL AND METHODS: Five patients, four females, and one male presented with failure to recognize reflected self-image, resulting in patients conversing with the image as a friend, fighting because the person in mirror is wearing her nose stud, suspecting the reflected self-image to be an intruder; but did not have prosopagnosia for others faces, non living objects on self and also apraxias except dressing apraxia in one patient. This phenomena is new to our knowledge. RESULTS: Mirror image agnosia is an unique phenomena which is seen in patients with parietal lobe atrophy without specificity to a category of dementing illness and seems to disappear as disease advances. DISCUSSION: Reflected self-images probably have a specific neural substrate that gets affected very early in posterior dementias specially the ones which predominantly affect the right side. At that phase most patients are mistaken as suffering from psychiatric disorder as cognition is moderately preserved. As disease becomes more widespread this symptom becomes masked. A high degree of suspicion and proper assessment might help physicians to recognize the organic cause of the symptom so that early therapeutic interventions can be initiated. Further assessment of the symptom with FMRI and PET scan is likely to solve the mystery of how brain handles reflected self-images. CONCLUSION: A new observation involving failure to recognize reflected self-images is reported.

Dataset Information

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image A?42 to the Natural l-Enantiomer.

Publications

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image Aβ42 to the Natural l-Enantiomer.

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