Advancements in nanotherapeutics for Alzheimer’s disease: current perspectives

Harilal, Seetha; Jose, Jobin; Parambi, Della Grace Thomas; Kumar, Rajesh; Mathew, Githa Elizabeth; Uddin, Sahab; Kim, Hoon; Mathew, Bijo

doi:10.1111/jphp.13132

Cited by 124 publications

(51 citation statements)

References 79 publications

(96 reference statements)

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“…In cases of AD and neuronal dysfunctions, there are several shreds of evidence denoting the vital contribution of Aβ [49,50]. An imbalance in Aβ formation and Aβ clearance [51,52] may occur in pathological and aging situations, for example, excitotoxicity and metabolic disorders, which can eventually lead to Aβ accumulation and the formation of senile plaques [53]. In case of AD, the disproportion of the level of Aβ might be because of its disturbance in generation and clearance in the brain.…”

Section: Amyloid Plaquesmentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

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Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

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Section: Amyloid Plaquesmentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

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“…[ 12 ] For these reasons, it has been suggested selective MAO‐B inhibitors might offer a potential means of treating AD. [ 13,14 ]…”

Section: Introductionmentioning

confidence: 99%

Design of enamides as new selective monoamine oxidase-B inhibitors

Kavully¹,

Dev³

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives To develop of new class of selective and reversible MAO-B inhibitors from enamides. Methods Syntheses of the titled derivatives (AD1-AD11) were achieved by reacting cinnamoyl chloride and various primary and secondary amines in basic medium. All eleven compounds were investigated for in vitro inhibitory activities against recombinant human MAO-A and MAO-B. The reversibilities of lead compound inhibitions were analysed by dialysis. MTT assays of lead compounds were performed using normal VERO cell lines. Key findings Compounds AD3 and AD9 exhibited the greatest inhibitory activity against MAO-B with IC 50 values of 0.11 and 0.10 µM, respectively, and were followed by AD2 and AD1 (0.51 and 0.71 µM, respectively). Most of the compounds weakly inhibited MAO-A, with the exceptions AD9 and AD7, which had IC 50 values of 4.21 and 5.95 µM, respectively. AD3 had the highest selectivity index (SI) value for MAO-B (>363.6) and was followed by AD9 (SI 42.1). AD3 and AD9 were found to be competitive inhibitors of MAO-B with K i values of 0.044 AE 0.0036 and 0.039 AE 0.0047 µM, respectively. Reversibility experiments showed AD3 and AD9 were reversible inhibitors of MAO-B; dialysis restored the activity of MAO-B to the reference level. MTT assays revealed AD3 and AD9 were non-toxic to normal VERO cell lines with IC 50 values of 153.96 and 194.04 µg/ml, respectively. Computational studies provided hypothetical binding modes for AD3 and AD9 in the binding cavities of MAO-A and MAO-B. Conclusions These results encourage further studies on the enamide scaffold as potential drug candidates for the treatment of Alzheimer's and Parkinson's diseases.

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“…Furthermore, these events should also be responsible for proteasome dysfunctions, and for an increase in NFTs and Aβ aggregates. 10 Besides these principal hypothesis, other mechanisms have been suggested in order to explain the pathophysiology of AD, 7 however, at now, none of them is exhaustive probably due to the fact that various simultaneous processes contribute to the high complexity of the disease.…”

Section: Ad Pathophysiological Main Hypothesismentioning

confidence: 99%

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Binda¹,

Murano²,

Rivolta³

2020

IJN

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The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.

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Advancements in nanotherapeutics for Alzheimer’s disease: current perspectives

Cited by 124 publications

References 79 publications

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Design of enamides as new selective monoamine oxidase-B inhibitors

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

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