| Autor: |
Bitan, G, Tarus, B, Vollers, SS, Lashuel, HA, Condron, MM, Straub, JE, Teplow, DB |
| Jazyk: |
angličtina |
| Rok vydání: |
2003 |
| Zdroj: |
Bitan, G; Tarus, B; Vollers, SS; Lashuel, HA; Condron, MM; Straub, JE; et al.(2003). A Molecular Switch in Amyloid Assembly: Met35and Amyloid β-Protein Oligomerization. Journal of the American Chemical Society, 125(50), 15359-15365. doi: 10.1021/ja0349296. UCLA: Retrieved from: http://www.escholarship.org/uc/item/03b6z9pt |
| Popis: |
Aberrant protein oligomerization is an important pathogenetic process in vivo. In Alzheimer's disease (AD), the amyloid β-protein (Aβ) forms neurotoxic oligomers. The predominant in vivo Aβ alloforms, Aβ40 and Aβ42, have distinct oligomerization pathways. Aβ42 monomers oligomerize into pentamer/hexamer units (paranuclei) which self-associate to form larger oligomers. Aβ40 does not form these paranuclei, a fact which may explain the particularly strong linkage of Aβ42 with AD. Here, we sought to determine the structural elements controlling paranucleus formation as a first step toward the development of strategies for treating AD. Because oxidation of Met35is associated with altered Aβ assembly, we examined the role of Met35in controlling Aβ oligomerization. Oxidation of Met35in Aβ42 blocked paranucleus formation and produced oligomers indistinguishable in size and morphology from those produced by Aβ40. Systematic structural alterations of the Cγ35-substituent group revealed that its electronic nature, rather than its size (van der Waals volume), was the factor controlling oligomerization pathway choice. Preventing assembly of toxic Aβ42 paranuclei through selective oxidation of Met35thus represents a potential therapeutic approach for AD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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