CE44 - Biochimie et chimie du vivant

Metal-based Agents for Selective Amyloid Imaging – MASAI

Submission summary

Amyloid aggregates are associated with many pathologies, like Alzheimers’s disease (AD) or Type 2 diabetes (T2DM), respectively involving Abeta and amylin. Recent evidence indicates a link between these two diseases, likely mediated by “cross-seeding” processes when one amyloid protein promotes aggregation of another. We identified the first metal complexes selective for amylin vs Abeta fibrils, and here we propose to i) improve their selectivity via rational molecular design, ii) investigate their peptide binding affinities, and iii) exploit their potential as imaging agents for selective MRI or SPECT visualisation of amyloid peptides in ex vivo tissue samples and preclinical models. These probes will help establish the role of peptide cross-seeding as the link between T2DM and AD. Ultimately, these results may explain why i) the presence of multiple amyloid proteins in tissues leads to exacerbation of clinical features, and ii) one amyloid disease is a risk factor for development of another.

Project coordination

Eva JAKAB TOTH (Centre national de la recherche scientifique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LCC Centre national de la recherche scientifique
Commissariat à l'énergie atomique et aux énergies alternatives
CBM Centre national de la recherche scientifique

Help of the ANR 570,345 euros
Beginning and duration of the scientific project: September 2022 - 48 Months

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