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Published on: May 22, 2018
Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein
Giuseppa Ida Grasso1, Francesco Bellia1, Giuseppe Arena2
1Institute of Biostructure and Bioimaging, National Research Council (CNR), via P. Gaifami 18, 95126, Catania, Italy.
Abstract:
Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated.
Insights
This study explores new trehalose-carnosine bio-conjugates as multi-functional agents to combat neurodegenerative disorders by reducing amyloid aggregation and oxidative stress from acrolein.
Area of Science:
- Neuroscience
- Biochemistry
- Materials Science
Background:
- Neurodegenerative disorders are linked to amyloid aggregates, metal ion imbalance, and oxidative stress.
- Acrolein, a biological oxidation product, plays a significant role in neurodegeneration.
- Multi-functional biomolecules offer a promising therapeutic strategy.
Purpose of the Study:
- To investigate novel trehalose-carnosine bio-conjugates for treating neurodegenerative diseases.
- To evaluate the antiaggregating, antioxidant, and antiglycating properties of these conjugates.
- To assess their capacity to sequester acrolein and inhibit protein aggregation.
Main Methods:
- Synthesis of a new trehalose-carnosine conjugate.
- Assessment of antiaggregating properties against self- and metal-induced aggregation.
- Evaluation of antioxidant effects and acrolein sequestration capabilities.
- Investigation of copper(II) coordination properties.
Main Results:
- The trehalose-carnosine conjugate demonstrated significant antiaggregating and antioxidant activities.
- The conjugate effectively sequestered acrolein, mitigating its toxicity.
- Copper(II) coordination properties were characterized, revealing potential therapeutic mechanisms.
Conclusions:
- Trehalose-carnosine bio-conjugates represent a promising therapeutic approach for neurodegenerative disorders.
- These multi-functional molecules address key pathological hallmarks including aggregation and oxidative stress.
- Further research into these conjugates could lead to novel treatments for brain diseases.
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