Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

Ashim Paul, Moran Frenkel-Pinter, Daniela Escobar Alvarez, Giulia Milordini, Ehud Gazit, Elsa Zacco, Daniel Segal

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

Self-assembly of proteins into amyloid fibrils is a hallmark of various diseases, including Alzheimer’s disease (AD) and Type-2 diabetes Mellitus (T2DM). Aggregation of specific peptides, like Aβ42 in AD and hIAPP in T2DM, causes cellular dysfunction resulting in the respective pathology. While these amyloidogenic proteins lack sequence homology, they all contain aromatic amino acids in their hydrophobic core that play a major role in their self-assembly. Targeting these aromatic residues by small molecules may be an attractive approach for inhibiting amyloid aggregation. Here, various biochemical and biophysical techniques revealed that a panel of tryptophan-galactosylamine conjugates significantly inhibit fibril formation of Aβ42 and hIAPP, and disassemble their pre-formed fibrils in a dose-dependent manner. They are also not toxic to mammalian cells and can reduce the cytotoxicity induced by Aβ42 and hIAPP aggregates. These tryptophan-galactosylamine conjugates can therefore serve as a scaffold for the development of therapeutics towards AD and T2DM.

اللغة الأصليةالإنجليزيّة
رقم المقال484
دوريةCommunications Biology
مستوى الصوت3
رقم الإصدار1
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 1 ديسمبر 2020

All Science Journal Classification (ASJC) codes

  • !!General Biochemistry, Genetics and Molecular Biology
  • !!General Agricultural and Biological Sciences
  • !!Medicine (miscellaneous)

بصمة

أدرس بدقة موضوعات البحث “Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity'. فهما يشكلان معًا بصمة فريدة.

قم بذكر هذا