Leuco Ethyl Violet as Self-Activating Prodrug Photocatalyst for In Vivo Amyloid-Selective Oxygenation.
Adv Sci (Weinh)
; 11(26): e2401346, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38689504
ABSTRACT
Aberrant aggregates of amyloid-ß (Aß) and tau protein (tau), called amyloid, are related to the etiology of Alzheimer disease (AD). Reducing amyloid levels in AD patients is a potentially effective approach to the treatment of AD. The selective degradation of amyloids via small molecule-catalyzed photooxygenation in vivo is a leading approach; however, moderate catalyst activity and the side effects of scalp injury are problematic in prior studies using AD model mice. Here, leuco ethyl violet (LEV) is identified as a highly active, amyloid-selective, and blood-brain barrier (BBB)-permeable photooxygenation catalyst that circumvents all of these problems. LEV is a redox-sensitive, self-activating prodrug catalyst; self-oxidation of LEV through a hydrogen atom transfer process under photoirradiation produces catalytically active ethyl violet (EV) in the presence of amyloid. LEV effectively oxygenates human Aß and tau, suggesting the feasibility for applications in humans. Furthermore, a concept of using a hydrogen atom as a caging group of a reactive catalyst functional in vivo is postulated. The minimal size of the hydrogen caging group is especially useful for catalyst delivery to the brain through BBB.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Alzheimer Disease
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Sci (Weinh)
/
Advanced science (Weinheim)
Year:
2024
Document type:
Article
Affiliation country:
Japón
Country of publication:
Alemania