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Potential therapeutics of Alzheimer's diseases: New insights into the neuroprotective role of trehalose‐conjugated beta sheet breaker peptides
Author(s) -
Di Natale G.,
Zimbone S.,
Bellia F.,
Tomasello M.F.,
Giuffrida M.L.,
Pappalardo G.,
Rizzarelli E.
Publication year - 2018
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 7
ISSN - 2475-8817
DOI - 10.1002/pep2.24083
Subject(s) - neuroprotection , peptide , amyloid beta , chemistry , trehalose , neurodegeneration , amyloid (mycology) , pharmacology , biochemistry , microbiology and biotechnology , neuroscience , biology , medicine , disease , inorganic chemistry
Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure. The conversion of the amyloid‐β (Aβ) peptide into soluble oligomers has recently become recognized as playing a key role in AD pathogenesis. Thus, prevention and therapeutic strategies against AD focus on modulating Aβ levels aiming also at stabilizing Aβ's monomeric status or inhibiting the peptide's self‐assembly. Peptide‐based inhibitors may provide a reasonable alternative to chemical small molecules. We report herein further insights into the neuroprotective action of two trehalose‐conjugated peptides able to counteract the Aβ's oligomers associated neuronal toxicity. In addition, the Trehalose‐Succinyl‐LPFFD‐NH 2 (Th‐Succ‐LPFFD‐NH 2 ) and Ac‐LPFFD‐Trehalose (Ac‐LPFFD‐Th) derivatives protect neuronal cells from excitotoxic insult mediated by NMDA and evoke by themselves pro‐survival signal pathways as an additional cell protective action. UHPLC‐HRMS experiments suggest that a possible step associated to the neuroprotective mechanism involves the cell uptake and/or a membrane interaction of the studied peptides.