Nanotechnology to improve the Alzheimer’s disease therapy with natural compounds

Ramalho, Maria João; Andrade, Stéphanie; Loureiro, Joana A.; Pereira, Maria do Carmo

doi:10.1007/s13346-019-00694-3

Cited by 52 publications

(38 citation statements)

References 186 publications

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“…The majority of the molecules tested in vivo could cross the BBB, as expected on the basis of their low molecular weight (<500 Da) (Ramalho et al, 2020). The comparative analysis of the concentrations detected in the brain is difficult and is hampered by the different methods and/or units employed by the authors.…”

Section: Ability Of Inhibitors To Cross Blood Brain Barrier and Stratmentioning

confidence: 99%

“…A few strategies have been employed to overcome these limitations and develop neuroprotective drugs, efficiently inhibiting Aβ oligomerization. The first consists in embedding the natural compounds in carriers to enhance bioavailability and direct their distribution toward brain tissue (Ramalho et al, 2020). The investigated drug delivery systems include polymer-based and lipid-based nanoparticles, together with microemulsions and nanoemulsions.…”

Section: Ability Of Inhibitors To Cross Blood Brain Barrier and Stratmentioning

confidence: 99%

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Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Pagano¹,

Tomaselli²,

Molinari³

et al. 2020

Front. Neurosci.

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Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with no cure and preventive therapy. Misfolding and extracellular aggregation of Amyloid-β (Aβ) peptides are recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and to the deposition of β-amyloid plaques in the brain, representing the hallmarks of AD. Given the urgent need to provide alternative therapies, natural products serve as vital resources for novel drugs. In recent years, several natural compounds with different chemical structures, such as polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received attention for their role against the neurodegenerative pathological processes. However, only for a small subset of them experimental evidences are provided on their mechanism of action. This review focuses on those natural compounds shown to interfere with Aβ aggregation by direct interaction with Aβ peptide and whose inhibitory mechanism has been investigated by means of biophysical and structural biology experimental approaches. In few cases, the combination of approaches offering a macroscopic characterization of the oligomers, such as TEM, AFM, fluorescence, together with high-resolution methods could shed light on the complex mechanism of inhibition. In particular, solution NMR spectroscopy, through peptide-based and ligand-based observation, was successfully employed to investigate the interactions of the natural compounds with both soluble NMR-visible (monomer and low molecular weight oligomers) and NMR-invisible (high molecular weight oligomers and protofibrils) species. The molecular determinants of the interaction of promising natural compounds are here compared to infer the chemical requirements of the inhibitors and the common mechanisms of inhibition. Most of the data converge to indicate that the Aβ regions relevant to perturb the aggregation cascade and regulate the toxicity of the stabilized oligomers, are the N-term and β1 region. The ability of the natural aggregation inhibitors to cross the brain blood barrier, together with the tactics to improve their low bioavailability are discussed. The analysis of the data ensemble can provide a rationale for the selection of natural compounds as molecular scaffolds for the design of new therapeutic strategies against the progression of early and late stages of AD.

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Section: Ability Of Inhibitors To Cross Blood Brain Barrier and Stratmentioning

confidence: 99%

Section: Ability Of Inhibitors To Cross Blood Brain Barrier and Stratmentioning

confidence: 99%

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Pagano¹,

Tomaselli²,

Molinari³

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

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“…The therapeutic opportunities for natural products in AD and its complications Therapeutic opportunities for natural products in AD Natural products are gaining increasing attention in AD therapy since there is almost no effective cure to date [104], and more than 100 natural compounds have been proposed as promising candidates for alleviating AD [105]. Indeed, approximately 46% new drugs that approved by FDA between 1981 and 2014 were from natural products and their derivatives [106].…”

Section: The Main Redox Signaling-associated Mechanisms and Their Cromentioning

confidence: 99%

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

Chen

Wang²,

Wang

et al. 2020

Biomark Res

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Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well. Graphical Abstract

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“…Nanoparticles have been developed to assist in drug delivery in a very broad range of pharmaceutical contexts, for example treating atherosclerosis (Lobatto et al, 2011;Chen J. et al, 2020;Ramalho et al, 2020) and other neurodegenerative diseases (Goldsmith et al, 2014), cardiovascular disease (Godin et al, 2010), diabetes (Veiseh et al, 2015), infections disease (Zhu et al, 2014;Zazo et al, 2016), protein drugs (Qin et al, 2019), and vaccine delivery (Pison et al, 2006;Zhao et al, 2014) in fact vaccine adjuvant development involves many of the same mechanisms as nanomedicine (Copland et al, 2005;Wang et al, 2019); it can be argued that it is only for historical reasons that it is not referred to as nanomedicine. The main application of nanomedicine is, however, cancer therapy (Tong and Kohane, 2016;Youn and Bae, 2018), particularly chemotherapy agent delivery, as this involves drugs with extremely high toxicity; targeted delivery, where the drug is kept from the rest of the body and the greatest possible fraction is delivered to the target tissue, in this case the tumor, is extremely desirable.…”

Section: Nanoparticle Design and Functionmentioning

confidence: 99%

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Bunker

Róg

2020

Front. Mol. Biosci.

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In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

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Nanotechnology to improve the Alzheimer’s disease therapy with natural compounds

Cited by 52 publications

References 186 publications

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

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