Leuco Ethyl Violet as Self‐Activating Prodrug Photocatalyst for In Vivo Amyloid‐Selective Oxygenation

Abstract: Aberrant aggregates of amyloid‐β (Aβ) 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 Aβ 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Leuco Ethyl Violet as Self‐Activating Prodrug Photocatalyst for In Vivo Amyloid‐Selective Oxygenation ; day:30 ; month:04 ; year:2024 ; extent:11
Advanced science ; (30.04.2024) (gesamt 11)

Urheber
Furuta, Masahiro
Arii, Suguru
Umeda, Hiroki
Matsukawa, Ryota
Shizu, Katsuyuki
Kaji, Hironori
Kawashima, Shigehiro A.
Hori, Yukiko
Tomita, Taisuke
Sohma, Youhei
Mitsunuma, Harunobu
Kanai, Motomu

DOI
10.1002/advs.202401346
URN
urn:nbn:de:101:1-2405011426376.734823632762
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
07.06.2025, 03:59 MESZ

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Beteiligte

  • Furuta, Masahiro
  • Arii, Suguru
  • Umeda, Hiroki
  • Matsukawa, Ryota
  • Shizu, Katsuyuki
  • Kaji, Hironori
  • Kawashima, Shigehiro A.
  • Hori, Yukiko
  • Tomita, Taisuke
  • Sohma, Youhei
  • Mitsunuma, Harunobu
  • Kanai, Motomu

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