Anti-neuroinflammatory, protective effects of the synthetic microneurotrophin BNN-20 in the advanced dopaminergic neurodegeneration of “weaver” mice

Panagiotakopoulou, Vasiliki; Botsakis, Konstantinos; Delis, Foteini; Mourtzi, Theodora; Tzatzarakis, Manolis; Dimopoulou, Aggeliki; Poulia, Nafsika; Αντωνίου, Κατερίνα; Stathopoulos, Georgios T.; Matsokis, Nikolaos; Charalampopoulos, Ioannis; Gravanis, Achilleas; Angelatou, Fevronia

doi:10.1016/j.neuropharm.2019.107919

Cited by 15 publications

(27 citation statements)

References 79 publications

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“…Our observation is also in accordance with recent studies suggesting an anti‐inflammatory and protective role of BNN20 in the advanced dopaminergic neurodegeneration of the weaver mutant mouse. In this study, BNN20 reduced the activation of pro‐inflammatory microglia inducing a shift in microglia polarization toward the anti‐inflammatory, neuroprotective phenotype (Panagiotakopoulou et al., 2020).…”

Section: Discussionmentioning

confidence: 53%

“…In this study, BNN20 reduced the activation of pro-inflammatory microglia inducing a shift in microglia polarization toward the antiinflammatory, neuroprotective phenotype (Panagiotakopoulou et al, 2020).…”

Section: Discussionmentioning

confidence: 53%

“…It was shown that BNN20 has a protective role regarding dopaminergic neurons, possibly, through TrkB in the weaver mouse mutant, which is a mouse model for Parkinson's disease (Botsakis et al, 2017). Moreover, recent studies showed that BNN20 has strong anti-inflammatory function, while being able to restore BDNF levels in this specific mouse model (Panagiotakopoulou et al, 2020).…”

Section: Significancementioning

confidence: 99%

“…In the present study, our aim was to elucidate the putative role of BNN20 in demyelination and remyelination, as a novel activator of both TrKA and TrkB, in contrast to the specific TrkA agonist, BNN27 (Botsakis et al., 2017; Panagiotakopoulou et al, 2020). As already known, there are plenty of models for studying demyelination and remyelination (Osorio‐Querejeta et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

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The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

Kalafatakis

Patellis

Charalampopoulos

et al. 2021

J of Neuroscience Research

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Myelin, produced by oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS), is an evolutionary trait of vertebrates contributing to action potential propagation over long distances. Myelin disruption occurs in demyelinating diseases and results in the cell death of either OLs or Schwann cells, leading to axonal demyelination and degeneration causing impairments in motor and cognitive function. There is a variety of demyelinating diseases with different

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 53%

Section: Significancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

Kalafatakis

Patellis

Charalampopoulos

et al. 2021

J of Neuroscience Research

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“…A new family of small synthetic molecules, C17‐spiro derivatives of dehydroepiandrosterone (DHEA) has been synthesized recently, 1 named microneurotrophins (MNTs) due to their ability to mimic some of the endogenous neurotrophins effects through the activation of specific neurotrophin receptors. Two of them, BNN27 [(R)‐3β,21‐ dihydroxy‐17 R ,20‐epoxy‐5‐pregnene] and BNN20 (17β‐spiro [5‐androstene‐17 2'oxiran]3β‐ol) (Figure 1), have exhibited anti‐apoptotic properties, in vitro 1,2 and in vivo 2‐5 . BNN27 is the molecule that has demonstrated specific properties regarding its binding to neurotrophin receptor and the subsequent biological actions, making it the lead molecule for the future development for potential therapeutic use.…”

Section: Introductionmentioning

confidence: 99%

Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

Tsika

Tzatzarakis

Antimisiaris

et al. 2021

Pharmacology Res & Perspec

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BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax) in the retina was detected at 2 h (tCtruemax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.

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The Interaction Between Nutraceuticals and Gut Microbiota: a Novel Therapeutic Approach to Prevent and Treatment Parkinson’s Disease

Yao,

Yang,

Yang

et al. 2024

Mol Neurobiol

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Anti-neuroinflammatory, protective effects of the synthetic microneurotrophin BNN-20 in the advanced dopaminergic neurodegeneration of “weaver” mice

Cited by 15 publications

References 79 publications

The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

The Interaction Between Nutraceuticals and Gut Microbiota: a Novel Therapeutic Approach to Prevent and Treatment Parkinson’s Disease

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