A Systematic Review of carbohydrate-based Bioactive Molecules for Alzheimer’s Disease

Abstract

The abundance, low cost, high density of functional groups and ease of purification of carbohydrates are among the most important features that make them a prime candidate for designing therapeutics. Several carbohydrate-based molecules, of both natural and synthetic origin, are known for their wide range of therapeutic activities. The incorporation of a carbohydrate moiety not only retains the pharmacological characteristics of a molecule but also improves its activity. Several sugar conjugates have been designed and reported to inhibit acetylcholinesterase, β-amyloid and tau aggregation. This systematic review provides a brief overview of carbohydrate-based bioactive molecules having anti-Alzheimer’s activity along with improved therapeutic potential. Most importantly, several reported carbohydrate-based molecules for Alzheimer’s disease act on β-amyloid aggregation, tau protein, cholinesterase and oxidative stress, with enhanced pharmacokinetic and mechanistic properties. The prospect of designing carbohydrate-based molecules for Alzheimer’s disease will definitely provide potential opportunities to discover novel carbohydrate-based drugs.

Synthesis and Potential Dual Inhibitory Activity Against Acetylcholinesterase and Butyrylcholinesterase of Galactose‐Conjugated Isatin β‐Thiosemicarbazones

“…AChE inhibitors had bonds with the enzyme peripheral binding site (PAS), and therefore, prevent the generation and deposition of Aβ [37] . The kinetic study above of AChE inhibition showed that our designed isatin β‐thiosemicarbazones could interact with PAS as well as CAS of AChE [2b,28a,38] . To further study of the dual action of these isatin derivatives, the amyloid‐beta protein (A β 1–42 ) anti‐aggregating activity of the most potent AChE inhibitors 4 s and 4 t was examined by the thioflavin‐T fluorescent (ThT) assay at 10 μM concentration.…”

“…Inhibitory properties of compounds on self‐induced and AChE induced aggregation of amyloid β protein 1–40 was determined using a thioflavin T (ThT)‐based fluorescence assay [28a] . The ThT excitation/ emission was measured at 448 nm/490 nm at 48 h using a multimode plate reader (BMG Labtech Omega FLUOstar).…”

“…Several sugar conjugates have been designed and reported for anti-Alzheimer's activity (acetylcholinesterase inhibition) along with improved therapeutic potential, with enhanced pharmacokinetic and mechanical properties. [28] For example, 2-(1,2,3,4tetrahydroacridin-9-yl)hydrazono-3-(2,3,4,6-tetra-O-acetyl-β-dgalactopyranosyl)-1,3-thiazolidin-4-one (F) is found to inhibit acetylcholinesterase with IC 50 = 0.14 � 0.02 μM in comparison with IC 50 = 0.03 � 0.01 μM of tacrine. [29] Iminosugar (deoxynojirimycin derivative) G is a strong low micromolar range, mixed inhibitor against AChE and BChE with IC 50 5.8 μM, K ia = 9.3 � 1.2 μM, K ib = 5.2 � 0.5 μM and IC 50 = 1.9 μM, K ia 5 1.4 � 0.4 μM, K ib = 4.5 � 1.4 μM, respectively.…”

Carriers and Antigens: New Developments in Glycoconjugate Vaccines

“…This included potential carrier proteins, adjuvants, and modifications of TACA antigens to improve stability, reduce hydrolytic cleavage and the cost of large-scale chemical or enzymatical synthesis [ 128 , 129 , 130 ]. Another area where carbohydrate-based conjugate vaccines find their application is the field of neurodegenerative diseases such as Alzheimer’s disease [ 131 ]. Overall, it cannot be denied that conjugate vaccines find their use in the broadest sense stretching multiple disease areas.…”

Recent Advances in the Development of Near-Infrared Fluorescent Probes for the in Vivo Brain Imaging of Amyloid-β Species in Alzheimer’s Disease

“…Curcumin derivatives were widely explored for their neuroprotection and therapeutic ability in neurodegenerative disorders and were found to have promising potential . The derivatives consist of a diketone structure alongside a trans double bond.…”