Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy

Jokar, Safura; Khazaei, Saeedeh; Behnammanesh, Hossein; Shamloo, Amir; Erfani, Mostafa; Beiki, Davood; Bavi, Omid

doi:10.1007/s12551-019-00606-2

Cited by 57 publications

(54 citation statements)

References 208 publications

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“…Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disorder characterized primarily by extracellular plaques of beta-amyloid peptide (Aβ) deposits and neurofibrillary tangles (NFTs) in the brain 1 . Majority of the strategies to combat AD have focused on inhibition of the amyloid aggregation, inhibition of γ -secretases, stabilization of the α -helical conformations, or elimination of the aggregated amyloid peptides 2 . Among these strategies, identification of inhibitors of Aβ aggregates has gained prominence as the origin of neurotoxicity is often associated with the aggregation process.…”

Section: Introductionmentioning

confidence: 99%

Disulfide-rich, cyclic peptides fromClitoria ternateaprotect against β-amyloid toxicity and oxidative stress in transgenicCaenorhabditis elegans

Kalmankar

Hari

Sowdhamini

et al. 2021

Preprint

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Neurotoxic aggregation of (Aβ) amyloid peptide is a hallmark of Alzheimers disease and increased reactive oxygen species (ROS) is known to be associated with this. Here, we report neuroprotective effects of disulfide-rich, circular peptides from Clitoria ternatea on Aβ induced toxicity in transgenic Caenorhabditis elegans. We show that cyclotide rich fractions from different plant tissues delay Aβ-induced paralysis in transgenic CL4176 strain expressing human muscle specific Aβ1-42 gene. It also improved Aβ induced defects in chemotaxis in CL2355 expressing Aβ1-42 in neuronal cells. ROS assay suggests that this is likely mediated by inhibition of Aβ oligomerization. Further, Aβ deposits were reduced in the strain, CL2006 treated with the fractions. Computational docking and molecular dynamics (MD) simulation support the findings since cyclotides bind effectively and stably to different forms of Aβ structures via hydrogen bonding and hydrophobic interactions. MD simulation further shows that cyclotides destabilize toxic amyloid assemblies. The study shows that cyclotides from C. ternatea could be a source of novel pharmacophore scaffold against neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Disulfide-rich, cyclic peptides fromClitoria ternateaprotect against β-amyloid toxicity and oxidative stress in transgenicCaenorhabditis elegans

Kalmankar

Hari

Sowdhamini

et al. 2021

Preprint

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“…3,4 In the past two decades, numerous strategies have been exercised to nd a cure for AD. 5 These strategies involve metal chelators, nanoparticles, the amyloidogenic core region (KLVFF) [6][7][8] or other fragments of the Ab peptide, 9,10 chemical chaperones, 11,12 peptide-based inhibitors, [13][14][15][16] small molecules, 5,17 and conformation-selective antibodies. [18][19][20][21] Antibody-based drug design is the most intriguing as antibodies engulf and eliminate the toxic Ab species.…”

Section: Introductionmentioning

confidence: 99%

An explicitly designed paratope of amyloid-β prevents neuronal apoptosis in vitro and hippocampal damage in rat brain

Paul

Kumar²,

Kalita

et al. 2021

Chem. Sci.

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“…Many amyloid inhibitors have been designed [ 24 ]. Historically, these inhibitors have been used to target pathogenic amyloids to treat neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Apomorphine Targets the Pleiotropic Bacterial Regulator Hfq

et al. 2021

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Hfq is a bacterial regulator with key roles in gene expression. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, thanks to its binding to small regulatory noncoding RNAs. This property is of primary importance for bacterial adaptation and survival in hosts. Small RNAs and Hfq are, for instance, involved in the response to antibiotics. Previous work has shown that the E. coli Hfq C-terminal region (Hfq-CTR) self-assembles into an amyloid structure. It was also demonstrated that the green tea compound EpiGallo Catechin Gallate (EGCG) binds to Hfq-CTR amyloid fibrils and remodels them into nonamyloid structures. Thus, compounds that target the amyloid region of Hfq may be used as antibacterial agents. Here, we show that another compound that inhibits amyloid formation, apomorphine, may also serve as a new antibacterial. Our results provide an alternative in order to repurpose apomorphine, commonly used in the treatment of Parkinson’s disease, as an antibiotic to block bacterial adaptation to treat infections.

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Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy

Cited by 57 publications

References 208 publications

Disulfide-rich, cyclic peptides fromClitoria ternateaprotect against β-amyloid toxicity and oxidative stress in transgenicCaenorhabditis elegans

Disulfide-rich, cyclic peptides fromClitoria ternateaprotect against β-amyloid toxicity and oxidative stress in transgenicCaenorhabditis elegans

An explicitly designed paratope of amyloid-β prevents neuronal apoptosis in vitro and hippocampal damage in rat brain

Apomorphine Targets the Pleiotropic Bacterial Regulator Hfq

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