Glucosamine and Its Analogues as Modulators of Amyloid-ß Toxicity.
ACS Med Chem Lett
; 12(4): 548-554, 2021 Apr 08.
Article
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| MEDLINE
| ID: mdl-33859794
ABSTRACT
In Alzheimer's disease (AD), amyloid-ß (Aß) oligomers are considered key mediators of synaptic dysfunction and cognitive impairment. These unstable intermediate Aß species can interfere with different cellular organelles, leading to neuronal cell death, through the formation of Ca2+-permeable membrane pores, impairment in the levels of acetylcholine neurotransmitters, increased insulin resistance, promotion of pro-inflammatory cascades, among others. Based on a series of evidences that indicate the key role of glycosaminoglycans (GAGs) in amyloid plaque formation, we evaluated the capacity of four monosaccharides, i.e., glucosamine (GlcN), N-acetyl glucosamine (GlcNAc), glucosamine-6-sulfate (GlcN6S), and glucosamine-6-phosphate (GlcN6P), to reduce the Aß-mediated pathological hallmarks. The tested monosaccharides, in particular, GlcN6S and GlcN6P, were able to interact with Aß aggregates, reducing neuronal cell death, Aß-mediated damage to the cellular membrane, acetylcholinesterase activity, insulin resistance, and pro-inflammation levels.
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01-internacional
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MEDLINE
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En
Revista:
ACS Med Chem Lett
Año:
2021
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Article