Phenolic Oxime Oligomers Inhibit Alzheimer's Amyloid Fibril Formation and Disaggregate Fibrils In Vitro

Dolphin, Gunnar T.; Renaudet, Olivier; Ouberaï, Myriam; Dumy, Pascal; Garcia, Julian; Reymond, Jean‐Louis

doi:10.1002/cbic.200900044

Cited by 6 publications

(6 citation statements)

References 36 publications

(43 reference statements)

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“…The design of novel polyphenol‐based or polyphenol‐inspired drugs against specific protein targets thus constitutes another promising direction for future research on polyphenols. Plant polyphenols have already started to inspire academic scientists in their quest for novel anticancer agents, more powerful natural product‐like antioxidants for use, for example, as food preservatives, and antifibrillogenic agents for the fight against neurodegenerative pathologies, as well as various functionalized materials that take advantage of the unique physicochemical properties of the phenol functional group 167. Many more exciting developments are certainly around the corner.…”

Section: What About the Future? Remaining Challenges …︁mentioning

confidence: 99%

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

et al. 2011

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Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.

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Section: What About the Future? Remaining Challenges …︁mentioning

confidence: 99%

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

et al. 2011

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“…Tetracycline(s) showed anti-amyloidogenic activity in vitro [1051] and protected Caenorhabditis elegans from A␤-induced toxicity by targeting oligomers [1052]. [745,1043,1095,1096,[1097][1098][1099][1100][1101][1102][1103][1104][1105] 2009: [1106][1107][1108][1109][1110][1111][1112][1113], 2010: [391,551,980,[1114][1115][1116][1117], 2011: [549,643,[1118][1119][1120][1121][1122] and 2012: [1033,[1123][1124][1125][1126][1127][1128][1129]1728].…”

Section: Drugs Preventing Amyloid-␤ Aggregationmentioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs

Froestl

Pfeifer

Muhs

2013

JAD

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Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

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“…As a consequence, considerable effort has been directed toward the identification of the substances able to reduce amyloid aggregation. In the past few years, a range of diverse small molecules have been found to inhibit or reduce the amyloid aggregation of various proteins, particularly in relation to Aβ deposition, the aggregation of transthyretin and the formation of protease-resistant forms of the prion protein [90-94]. Kim [93] investigated the effect of several classes of naturally occurring compounds on Aβ amyloid aggregation.…”

Section: Tacrine and Anti-amyloid Aggregationmentioning

confidence: 99%

“…Doplhin et al . [94] demonstrated that longer trioxime oligomers showed an effective reduction of Aβ amyloid fibrils formation. One of the first compounds to be identified with blocked tau-tau interaction was the phenothiazine methylene blue [95].…”

Section: Tacrine and Anti-amyloid Aggregationmentioning

confidence: 99%

Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation and Neuroprotective Properties

et al. 2011

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The review summarizes research into the highly relevant topics of cholinesterase and amyloid aggregation inhibitors connected to tacrine congeners, both of which are associated with neurogenerative diseases. Various opinions will be discussed regarding the dual binding site inhibitors which are characterized by increased inhibitor potency against acetylcholin/butyrylcholine esterase and amyloid formation. It is suggested that these compounds can both raise levels of acetylcholine by binding to the active site, and also prevent amyloid aggregation. In connection with this problem, the mono/dual binding of the multifunctional derivatives of tacrine, their mode of action and their neuroprotective activities are reported. The influence of low molecular compounds on protein amyloid aggregation, which might be considered as a potential therapeutic strategy in the treatment of Alzheimer's disease is also reported. Finally, attention is paid to some physico-chemical factors, such as desolvation energies describing the transfer of the substrate solvated by water, the metal-chelating properties of biometals reacting with amyloid precursor protein, amyloid beta peptide and tau protein.

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Phenolic Oxime Oligomers Inhibit Alzheimer's Amyloid Fibril Formation and Disaggregate Fibrils In Vitro

Cited by 6 publications

References 36 publications

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs

Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation and Neuroprotective Properties

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