FGFs and their receptors, in vitro and in vivo studies: New FGF receptor in the brain, FGF-1 in muscle, and the use of functional analogues of low-affinity heparin-binding growth factor receptors in tissue repair

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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Controlled Release of Endothelial Cell Growth Factor from Chitosan-Albumin Microspheres for Localized Angiogenesis: In Vitro and in Vivo Studies

Artificial Cells Blood Substitutes and Biotechnology ◽

10.3109/10731199609117438 ◽

1996 ◽

Vol 24 (3) ◽

pp. 257-271 ◽

Cited By ~ 46

Author(s):

Y. Murat Elçin ◽

Vivek Dixit ◽

Gary Gitnick

Keyword(s):

Endothelial Cell ◽

Controlled Release ◽

Growth Factor ◽

Cell Growth ◽

In Vivo Studies ◽

Albumin Microspheres ◽

Endothelial Cell Growth Factor ◽

Endothelial Cell Growth

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Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Biology ◽

10.3390/biology9070161 ◽

2020 ◽

Vol 9 (7) ◽

pp. 161

Author(s):

Séverine André ◽

Lionel Larbanoix ◽

Sébastien Verteneuil ◽

Dimitri Stanicki ◽

Denis Nonclercq ◽

...

Keyword(s):

Ldl Receptor ◽

Density Lipoprotein ◽

Therapeutic Agents ◽

In Vivo Studies ◽

Phage Display Technology ◽

Brain Penetration ◽

Wide Range ◽

The Brain

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.

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Boosting GSH Using the Co-Drug Approach: I-152, a Conjugate of N-acetyl-cysteine and β-mercaptoethylamine

Nutrients ◽

10.3390/nu11061291 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1291 ◽

Cited By ~ 5

Author(s):

Rita Crinelli ◽

Carolina Zara ◽

Michaël Smietana ◽

Michele Retini ◽

Mauro Magnani ◽

...

Keyword(s):

Cell Cultures ◽

In Vivo Studies ◽

In Vivo Metabolism ◽

Pharmacokinetic Properties ◽

Immunomodulatory Properties ◽

Acetyl Cysteine ◽

High Doses ◽

The Brain

Glutathione (GSH) has poor pharmacokinetic properties; thus, several derivatives and biosynthetic precursors have been proposed as GSH-boosting drugs. I-152 is a conjugate of N-acetyl-cysteine (NAC) and S-acetyl-β-mercaptoethylamine (SMEA) designed to release the parent drugs (i.e., NAC and β-mercaptoethylamine or cysteamine, MEA). NAC is a precursor of L-cysteine, while MEA is an aminothiol able to increase GSH content; thus, I-152 represents the very first attempt to combine two pro-GSH molecules. In this review, the in-vitro and in-vivo metabolism, pro-GSH activity and antiviral and immunomodulatory properties of I-152 are discussed. Under physiological GSH conditions, low I-152 doses increase cellular GSH content; by contrast, high doses cause GSH depletion but yield a high content of NAC, MEA and I-152, which can be used to resynthesize GSH. Preliminary in-vivo studies suggest that the molecule reaches mouse organs, including the brain, where its metabolites, NAC and MEA, are detected. In cell cultures, I-152 replenishes experimentally depleted GSH levels. Moreover, administration of I-152 to C57BL/6 mice infected with the retroviral complex LP-BM5 is effective in contrasting virus-induced GSH depletion, exerting at the same time antiviral and immunomodulatory functions. I-152 acts as a pro-GSH agent; however, GSH derivatives and NAC cannot completely replicate its effects. The co-delivery of different thiol species may lead to unpredictable outcomes, which warrant further investigation.

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Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1611769113 ◽

2016 ◽

Vol 113 (50) ◽

pp. E8169-E8177 ◽

Cited By ~ 59

Author(s):

Sung Il Park ◽

Gunchul Shin ◽

Jordan G. McCall ◽

Ream Al-Hasani ◽

Aaron Norris ◽

...

Keyword(s):

Radio Frequency ◽

Antenna Arrays ◽

Capacitive Coupling ◽

Radio Frequency Power ◽

In Vivo Studies ◽

Active Motion ◽

The Brain ◽

Frequency Power

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless μ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor μ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different μ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.

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Heparin-binding epidermal growth factor-like growth factor: a component in chromaffin granules which promotes the survival of nigrostriatal dopaminergic neurones in vitro and in vivo

Neuroscience ◽

10.1016/j.neuroscience.2003.12.033 ◽

2004 ◽

Vol 124 (4) ◽

pp. 757-766 ◽

Cited By ~ 21

Author(s):

M. Hanke ◽

L.M. Farkas ◽

M. Jakob ◽

R. Ries ◽

J. Pohl ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Heparin Binding ◽

Chromaffin Granules ◽

Epidermal Growth

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Effects of AMP-Activated Protein Kinase in Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2009.255 ◽

2009 ◽

Vol 30 (3) ◽

pp. 480-492 ◽

Cited By ~ 104

Author(s):

Jun Li ◽

Louise D McCullough

Keyword(s):

Protein Kinase ◽

In Vivo Studies ◽

Ampk Activation ◽

Vigorous Exercise ◽

Nitric Oxide Signaling ◽

Reductase Inhibitors ◽

Amp Activated Protein Kinase ◽

The Brain

AMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK is found in most mammalian tissues including the brain. As a key metabolic and stress sensor/effector, AMPK is activated under conditions of nutrient deprivation, vigorous exercise, or heat shock. However, it is becoming increasingly recognized that changes in AMPK activation not only signal unmet metabolic needs, but also are involved in sensing and responding to ‘cell stress’, including ischemia. The downstream effect of AMPK activation is dependent on many factors, including the severity of the stressor as well as the tissue examined. This review discusses recent in vitro and in vivo studies performed in the brain/neuronal cells and vasculature that have contributed to our understanding of AMPK in stroke. Recent data on the potential role of AMPK in angiogenesis and neurogenesis and the interaction of AMPK with 3-hydroxy-3-methy-glutaryl-CoA reductase inhibitors (statins) agents are highlighted. The interaction between AMPK and nitric oxide signaling is also discussed.

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