Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models

Iyaswamy, Ashok; Wang, Xueli; Krishnamoorthi, Senthilkumar; Kaliamoorthy, Venkatapathy; Sreenivasmurthy, Sravan Gopalkrishnashetty; Durairajan, Siva Sundara Kumar; Song, Ju‐Xian; Tong, Benjamin Chun‐Kit; Zhu, Zhou; Su, Cheng-Fu; Liu, Jia; Cheung, King‐Ho; Lu, Jiahong; Tan, Jieqiong; Li, Hung‐Wing; Wong, Man; Li, Min

doi:10.1016/j.redox.2022.102280

Cited by 49 publications

(55 citation statements)

References 38 publications

(66 reference statements)

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“…It is an age-related disorder that is accompanied by a loss of memory and has manifestations like congestive heart failure. It is characterized by recent memory loss in the early stages accompanied by a profound cognitive decline in the later stages (Iyaswamy et al, 2022 ). Behavioral issues, loss of working abilities, impaired communication skills, poor reasoning power, and loss of personality traits are other hallmarks of this neurodegenerative disorder (Sreenivasmurthy et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics

Arora

Bhatt²,

Kumar³

et al. 2022

Front. Aging Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310–3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics

Arora

Bhatt²,

Kumar³

et al. 2022

Front. Aging Neurosci.

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“…Cocoa is known to contain many phytochemicals such as polyphenols, flavanols such as epicatechin and catechin, as well as procyanidins [ 43 ]. In fact, several evidence have confirmed that such natural compounds have not only antioxidant but also anti-neuroinflammatory activity and are able to attenuate neurological disorders [ 54 , 67 , 68 , 69 , 70 ]. However, it is reported that cocoa compounds can induce neuronal protection mostly for their efficacy on endothelial cells, in which they stimulate NO synthesis enhancing cerebrovascular circulation [ 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Antigen-antibody complexes were detected by enhanced chemiluminescence (ECL kit, Amersham, Germany). Filters were exposed to LAS 4000 (GE Healthcare, Chicago, IL, USA) and the densitometry analysis of autoradiographs was performed by the ImageJ program, version 1.47 ( , accessed on 1 February 2022) [ 54 ].…”

Section: Methodsmentioning

confidence: 99%

Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK

et al. 2022

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Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson’s disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD.

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“…Equal amounts of protein were loaded onto 6–12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels and transferred to polyvinylidene fluoride (PVDF) membranes (Merck Millipore, Darmstadt, Germany), and blocked with 5% non-fat dry milk in Tris-buffered saline (25 mM Tris, 2.7 mM KCl, 137 mM NaCl, and 0.1% Tween-20; pH 7.4). The complete experimental procedure is previously described [ 25 ]. In brief, after blocking, the membrane was incubated with target primary antibodies overnight in a cold room at 4 °C with constant shaking.…”

Section: Methodsmentioning

confidence: 99%

Cytosolic HMGB1 Mediates LPS-Induced Autophagy in Microglia by Interacting with NOD2 and Suppresses Its Proinflammatory Function

Kim

Seol

et al. 2022

Cells

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The high mobility group box 1 (HMGB1), a well-known danger-associated molecule pattern (DAMP) molecule, is a non-histone chromosomal protein localized in the nucleus under normal physiological conditions. HMGB1 exhibits diverse functions depending on its subcellular location. In the present study, we investigated the role of HMGB1-induced autophagy in the lipopolysaccharide (LPS)-treated BV2 microglial cell line in mediating the transition between the inflammatory and autophagic function of the nucleotide-binding oligomerization domain-containing 2 (NOD2), a cytoplasmic pattern-recognition receptor. The induction of the microtubule-associated protein 1 light chain 3 (LC3), an autophagy biomarker, was detected slowly in BV2 cells after the LPS treatment, and peak induction was detected at 12 h. Under these conditions, NOD2 level was significantly increased and the binding between HMGB1 and NOD2 and between HMGB1 and ATG16L1 was markedly enhanced and the temporal profiles of the LC3II induction and HMGB1-NOD2 and HMGB1-ATG16L1 complex formation coincided with the cytosolic accumulation of HMGB1. The LPS-mediated autophagy induction was significantly suppressed in BV2 cells after HMGB1 or NOD2 knock-down (KD), indicating that HMGB1 contributes to NOD2-mediated autophagy induction in microglia. Moreover, NOD2-RIP2 interaction-mediated pro-inflammatory cytokine induction and NF-κB activity were significantly enhanced in BV2 cells after HMGB1 KD, indicating that HMGB1 plays a critical role in the modulation of NOD2 function between pro-inflammation and pro-autophagy in microglia. The effects of the cell-autonomous pro-autophagic pathway operated by cytoplasmic HMGB1 may be beneficial, whereas those from the paracrine pro-inflammatory pathway executed by extracellularly secreted HMGB1 can be detrimental. Thus, the overall functional significance of HMGB1-induced autophagy is different, depending on its temporal activity.

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Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models

Cited by 49 publications

References 38 publications

RETRACTED: QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics

RETRACTED: QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics

Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK

Cytosolic HMGB1 Mediates LPS-Induced Autophagy in Microglia by Interacting with NOD2 and Suppresses Its Proinflammatory Function

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