Novel therapeutic strategies for Alzheimer's disease: Implications from cell-based therapy and nanotherapy

Derakhshankhah, Hossein; Sajadimajd, Soraya; Jafari, Samira; Izadi, Zhila; Sarvari, Sajad; Sharifi, Majid; Falahati, Mojtaba; Moakedi, Faezeh; Muganda, Willis Collins Akeyo; Müller, Mareike; Raoufi, Mohammad; Presley, John F.

doi:10.1016/j.nano.2020.102149

Cited by 36 publications

(39 citation statements)

References 172 publications

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“…AD is a complicated neurodegenerative disease clinically characterized by a progressive loss of cognition (Derakhshankhah et al, 2020). The pathological hallmarks of the disease include extracellular aggregates of Aβ and tau-associated pathology.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

Wang

et al. 2020

Front. Cell. Neurosci.

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Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are promising for the treatment of Alzheimer's disease (AD). However, their low rate of migration and survival in the brain limit their clinical applicability. This study is designed to improve the therapeutic potential of hUC-MSCs by preincubating them with resveratrol, a natural polyphenol capable of regulating cell destiny. Herein, we demonstrate that resveratrol preincubation enhances the migration of hUC-MSCs in vitro, as well as their survival and homing into the hippocampus of AD mice in vivo. Moreover, resveratrol-primed MSCs were better able to inhibit amyloid-β peptide (Aβ) deposition, Tau hyperphosphorylation, and oxidative stress, all while improving learning and memory. Notably, we found that hUC-MSCs inhibited neuroinflammation by reacting with astrocytes and microglial cells and suppressing mitogen-activated protein kinases (MAPKs), extracellular signal kinases (ERK), p38 kinases (p38), and c-Jun N-terminal kinases (JNK) signaling pathways in the hippocampus of AD mice. Furthermore, resveratrol pretreatment enhanced these effects. Conclusively, the current study revealed that resveratrol preconditioning protected hUC-MSCs against the hostile microenvironment characteristic of AD and enhanced their viability and homing into the brain of AD mice. The use of resveratrol-pretreated hUC-MSCs is thereby proposed to be a promising therapy for AD.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

Wang

et al. 2020

Front. Cell. Neurosci.

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“…A rapid and successful development of cell-replacement therapies (e.g., application of multipotent stem cells) is expected for AD treatment [232].…”

Section: Discussionmentioning

confidence: 99%

Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis

2020

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The structural polymorphism and the physiological and pathophysiological roles of two important proteins, β-amyloid (Aβ) and tau, that play a key role in Alzheimer’s disease (AD) are reviewed. Recent results demonstrate that monomeric Aβ has important physiological functions. Toxic oligomeric Aβ assemblies (AβOs) may play a decisive role in AD pathogenesis. The polymorph fibrillar Aβ (fAβ) form has a very ordered cross-β structure and is assumed to be non-toxic. Tau monomers also have several important physiological actions; however, their oligomerization leads to toxic oligomers (TauOs). Further polymerization results in probably non-toxic fibrillar structures, among others neurofibrillary tangles (NFTs). Their structure was determined by cryo-electron microscopy at atomic level. Both AβOs and TauOs may initiate neurodegenerative processes, and their interactions and crosstalk determine the pathophysiological changes in AD. TauOs (perhaps also AβO) have prionoid character, and they may be responsible for cell-to-cell spreading of the disease. Both extra- and intracellular AβOs and TauOs (and not the previously hypothesized amyloid plaques and NFTs) may represent the novel targets of AD drug research.

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“…Because of these favorable properties, polyphenols or their synthetic analogs can potentially serve as nontoxic therapeutic candidates in the prevention and management of AD and other neurological disorders. Furthermore, polyphenolic compounds, such as curcumin, can be incorporated into polymeric nanoparticles-for example, those based on poly(ethylene glycol) (PEG), poly(lactic acid) (PLA), poly(ethyleneimine) (PEI), poly(lactic-coglycolic acid) (PLGA), chitosan, and poly(vinylpyrrolidone) (PVP), to enhance their blood-brain barrier (BBB) permeability [63]. Curcumin-PEG-PLA nanoparticles, for example, cross the BBB six- Chlorogenic acid-derived catabolites, such as dihydrocaffeic acid, dihydroferulic acid and feruloylglycine, were also shown to be effective neuroprotectors [45].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, polyphenolic compounds, such as curcumin, can be incorporated into polymeric nanoparticles-for example, those based on poly(ethylene glycol) (PEG), poly(lactic acid) (PLA), poly(ethyleneimine) (PEI), poly(lactic-co-glycolic acid) (PLGA), chitosan, and poly(vinylpyrrolidone) (PVP), to enhance their blood-brain barrier (BBB) permeability [63]. Curcumin-PEG-PLA nanoparticles, for example, cross the BBB six-fold more effectively as compared to the curcumin alone [63,64]. Thus, gut bacterial metabolism-derived polyphenolic compounds, in nanoparticulate form, may prove to be effective therapeutics for AD and other neurological disorders, such as TBI and PD.…”

Section: Discussionmentioning

confidence: 99%

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

et al. 2020

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Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

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Novel therapeutic strategies for Alzheimer's disease: Implications from cell-based therapy and nanotherapy

Cited by 36 publications

References 172 publications

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

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