BIOGRAPHENE

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of Neurodegenerative Diseases
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[New Scientist] Quantum dots in brain could treat Parkinson’s and Alzh…
Tiny particles called quantum dots reduce symptoms in mice primed to develop a type of Parkinson’s disease, and also block formation of the toxic protein clumps in Alzheimer’s. They could one day be a novel treatment for these brain disorders, although tests in people are some years away. Quantum dots are just a few nanometres in size – so small they become subject to some of the strange effects of quantum physics. They have useful electronic and fluorescent properties and are found in some TV screens and LED lights. Unlike most medicines, their tiny size means they can pass from bloodstream into the brain. Byung Hee Hong of Seoul National University in the South Korea and his colleagues wondered if they would affect the molecules involved in Parkinson’s or other brain disorders. Parkinson’s disease involves gradually worsening tremors and movement problems. It is thought to be caused by a protein called synuclein found in nerve cells folding into the wrong shape, which triggers a chain reaction of misfolding in nearby synuclein molecules. This leads to a build-up of long strands or “fibrils” of the protein, killing neurons. Quantum surprise Hong’s team found that in a dish, quantum dots made from graphene – a form of carbon – bind to synuclein, and not only stop it from clumping into fibres, but also cause existing fibres to break up into individual molecules. “We didn’t expect the quantum dots to induce disaggregation of fibrils,” says Hong. Next the team injected quantum dots into mice dosed with fibrils, which normally trigger gradually worsening movement problems. Six months later, the mice showed improvement on two different physical tests. If the treatment affects people the same way, Hong says it is unclear how much benefit this would bring. “It’s hard to translate the results in mice to actual patients, whose systems are way more complicated. But we do believe quantum dots can make positive impacts to some extent.” Read more: Parkinson’s disease may start in the gut and travel to the brain Another team has found that quantum dots show promise for Alzheimer’s disease; in a similar fashion, they bind to a protein called amyloid, and reduce it from clumping together, a process thought to be involved in this dementia. However tests in an animal version of Alzheimer’s haven’t yet been reported. “This might be a universal effect on any kind of fibrillation process related to disease,” says Hong. His team is investigating using quantum dots in Alzheimer’s and motor neuron disease – the condition that affected Stephen Hawking – which also involves protein clumping. Sebastien Paillusson of King’s College London, who was not involved in the work, says the findings in mice are promising, but should not raise anyone’s hopes until the approach has been tested in people. “Unfortunately in Parkinson’s there have been a lot of compounds shown to work in mice but not in humans.” Paillusson added, though, that it was unusual for anything to reverse the fibre-forming process. “This is a very novel approach.” Hong says if safety tests in animals go well, they hope to start trials in people in about two years. Journal reference: Nature Nanotechnology, DOI: 10.1038/s41565-018-0179-y Read more: https://www.newscientist.com/article/2173740-quantum-dots-in-brain-could-treat-parkinsons-and-alzheimers-diseases/#ixzz62EyEGZAG
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[Physics World] Could graphene quantum dots help treat Parkinson’s disease?
Quantum dots made from the carbon material graphene prevent alpha-synuclein from aggregating into strand-like structures known as fibrils. They also help disaggregate fibrils that have already formed. Alpha-synuclein fibrils are thought to be implicated in Parkinson’s disease because they kill dopamine-generating neurons, so the new findings might help in the development of therapies to treat this disease as well as others in which fibrilization occurs. Synucleins are a family of proteins typically found in neural tissue. Researchers believe that one type of synuclein, alpha-synuclein, twists into fibrils, which then accumulate in the midbrain of patients with Parkinson’s. Treatments with efficient anti-aggregation agents might thus be one way of fighting the disease. A team led by Byung Hee Hong of Seoul National University and Han Seok Ko of The Johns Hopkins University in Baltimore have now found that graphene quantum dots (GQDs) bind to alpha-synuclein in vitro. Thanks to fluorescence and turbidity assays, as well as transmission electron microscopy measurements, the researchers found that the dots prevent alpha-synuclein from forming into fibrils. The nanostructures also dissociate already-formed fibrils into short fragments, with the average length of the fragments shortening from 1 micron to 235 nm and 70 nm after 6 and 24 hours respectively. The number of fragments starts to decrease after three days too and cannot be detected at all after seven days, which implies that the fibrils completely disintegrate after this time. Mice show improved symptoms of the disease after six months In their experiments, Hong and Ko’s team also injected the GQDs into the bloodstream of transgenic mice with Parkinson’s and found that they showed improved symptoms of the disease after six months – as assessed by routine cylinder and pole tests. The mice showed fewer movement problems, were able to use both forepaws to balance themselves on cylinders and ran down poles quicker. The researchers say that these improvements could come from the fact that the quantum dots are small enough to penetrate the blood-brain barrier and protect against dopamine neuron loss induced by alpha-synuclein preformed fibrils. The GQDs do not show any appreciable in vitro and in vivo toxicity after six months of “prolonged injection” either and can be cleared from the body and excreted into urine, they add. The quantum dots might produce a similar effect in other diseases in which fibrilization occurs. Indeed, previous research by another team has already shown that injecting them into mice with Alzheimer’s inhibits the fibrilization of beta-amyloid peptides. Full details of the research have been published in Nature Nanotechnology 10.1038/s41565-018-0179-y. Source: https://physicsworld.com/a/could-graphene-quantum-dots-help-treat-parkinsons-disease/
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[AlzForum] Nano-size Quantum Dots Bust Up Synuclein Pathology
13 Jul 2018 Best known to biologists as brightly glowing florescent tracers, quantum dots could also have therapeutic powers, says a new study. Work led by Han Seok Ko of Johns Hopkins University in Baltimore and Byung Hee Hong at the University of Seoul, South Korea, reveals that nano-scale carbon lattices bind to and dissolve α-synuclein fibers in vitro. In cells, the graphene quantum dots protect against α-synuclein toxicity, and prevent its spread between neurons. In animals, the dots protect neurons from the ravages of injected synuclein fibrils, or mutant synuclein expression, all without signs of toxicity. The findings are reported in the July 9 Nature Nanotechnology. Quantum dots made from graphene disaggregate α-synuclein fibers in vitro. In animals, the dots prevent α-synucleinopathy and improve motor function. Nanomaterials could provide new approaches to neuroprotection. “This exciting study presents a novel and very untraditional way of treating synucleinopathy,” said Poul Henning Jensen, Aarhus University in Denmark. “They have done a good job of documenting their observation of a protective effect, but understanding the mechanism will take more work,” he said. Quantum dots can be made of many materials—those derived from graphene (GQDs) consist of a single layer of carbon atoms arranged in a hexagonal lattice, sometimes with chemical modifications. GQDs look like small scraps of chicken wire, and are being developed as biosensors, imaging agents, and carriers for drug delivery. Interest in these nanostructures as therapeutic agents is on the rise. Some reports suggest they interfere with amyloid fiber formation, and disaggregate Aβ or α-synuclein fibrils (Mahmoudi et al., 2012; Li et al., 2014; Liu et al., 2015; Yang et al., 2015; Liu et al., 2018). Plane of Attack. In a molecular simulation, carboxyl groups (red) on a graphene quantum dot (gray lattice) bind to the amyloid core of α-synuclein fibril (tan), and unfold it via hydrophobic interactions. [Courtesy of Kim et al., 2018 Nature Nanotechnology.] In the new study, co-first authors Donghoon Kim and Je Min Yoo tested the ability of chemically modified GQDs to counteract the aggregation, transmission, and toxicity of α-synuclein. By treating pure carbon fibers with strong acid, the investigators generated 2 nm square snippets of graphene that sport carboxylic acid groups around their edges. When mixed in equal amounts with purified α-synuclein in vitro, these GQDs potently inhibited fibril formation. Even more, they rapidly dissolved preformed fibrils, first melting the structures into shorter fragments and then into monomers. Structural analysis with NMR and other techniques indicated that the GQDs’ negatively charged carboxyl groups bound to the positively charged N-terminal region of α-synuclein in fibrils. A molecular dynamics simulation predicted that hydrophobic interactions between valine residues in α-synuclein and the GQD lattice destroy the β-sheet structure, driving fibril dissociation (see image at right). In agreement with that idea, removing the carboxyl groups destroyed the GQDs’ fibril-busting activity. Moving to cell-based assays, the scientists demonstrated that GQDs protected primary cortical neurons from α-synuclein toxicity. The dots prevented cell death, restored neurite outgrowth and synaptic proteins, and mitigated mitochondrial toxicity induced by α-synuclein preformed fibrils (PFFs). Quantum dots also reduced the accumulation of phosphorylated and aggregated α-synuclein in response to PFFs, and blocked the transmission of α-synuclein pathology from cell to cell in vitro. Protection appeared to occur inside cells: In live imaging experiments, PFFs and GQDs were spotted together in lysosomes. There, the signal for PFFs decreased and that for GQDs increased over time, suggesting disaggregation of α-syn takes place in that compartment. The protective effects of GQDs extended to two different PD mouse models. In one, the researchers injected α-syn PFFs into the striata of wild-type mice. After 180 days, six mice lost about half of their dopamine neurons, whereas six animals also given GQD injections twice a week lost only about one-quarter. Treatment also reduced the spread of gliosis, pathologic phosphorylated α-synuclein, and Lewy body-like inclusions (see image below). The animals’ motor function improved too. GQD-treated mice had more control of their paws and balanced better on a pole. In a transgenic PD model, pathology and motor function improved when mice expressing A53T mutated human α-synuclein were treated with the GQDs. Nano Defense. In wild-type mice, the spread of α-synuclein fibrils caused by striatal injection of PFFs (top) is mitigated by GQDs (bottom). [Courtesy of Kim et al., 2018 Nature Nanotechnology.] The graphene dots even appeared safe. After four months of dosing, they caused no apparent harm to the mice. They were cleared in the urine. Multiple carboxyl groups packed onto teeny, inert scaffolds provide a potent, nontoxic, anti-aggregation agent, the authors concluded. How did GQDs get into the brain? The dots readily traversed layers of endothelial cells and astrocytes in an in vitro model of the blood-brain barrier. Fluorescent imaging showed both cell types accumulated GQDs in lysosomes and released them via exosomes. The scientists propose that GQDs are endocytosed by endothelial cells, then released via exosomes, to be taken up by astrocytes, and finally released into the brain. In vivo, the researchers detected GQDs widely in the central nervous system after intraperitoneal injection. Given studies suggesting they disassemble Aβ fibrils, these quantum dots might have applications beyond tackling synuclein fibrillogenesis. Ko told Alzforum they have confirmed that their GQDs can dissociate Aβ fibrils and oligomers in vitro. They are now testing the dots in a mouse model of AD, he said. At the same time, they are moving forward on the Parkinson’s disease front. Hong is working on safety studies in animals as a prelude to human use. “If all goes well we hope to start trials in people within two years,” Ko said. He believes GQDs will have a universal effect on neurodegenerative disorders that involve accumulation of fibrillar aggregates. “This paper opens a new research direction on chemical modified nanomaterial for anti-amyloid therapy,” wrote Mingdong Dong, Aarhus University, Denmark, in an email to Alzforum. Dong’s group is evaluating other nanomaterial as anti-amyloid agents (Wang et al., 2018). Jensen agreed, adding that he hopes the authors will clearly explain the procedure for making the dots. “I’m sure this paper will stimulate at lot of other studies. Their data suggest that it is important to produce the quantum dots in a specific way, and I hope they will describe the method in detail. If there is a trick to the production, it is important to document that,” he said. Jensen also told Alzforum he’d like to see more quantitation of the interaction between GQDs and fibrils, including measures of affinity and specificity for other amyloids, including nonpathogenic, physiological forms.—Pat McCaffrey
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Tiny Particles Prevent Neuronal Loss, Improve Motor Symptoms in Parkinson's Patients
JULY 13, 2018 Jose Marques Lopes, PhD Tiny crystals known as quantum dots can block the formation of Parkinson’s hallmark protein clumps, lowering nerve cell death and motor deficits, a mouse study has found. The research, “Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease,” was published in Nature Nanotechnology. Quantum dots are very small, engineered crystals with a diameter of as few as 10 to 100 atoms. They have electronic and fluorescent properties that have been used in research. The particles are found in some TV screens, LED lights and solar cells. Because of their very small size, these particles, unlike most medicines, can bypass the blood-brain-barrier, a semipermeable membrane that protects the brain from outside circulation. Parkinson’s patients typically have protein deposits in their nerve cells, called Lewy bodies. There are protein clumps composed mainly of misfolded alpha-synuclein protein that form long strands, or fibrils, and lead to the progressive loss of dopamine-producing neurons in an area of the brain called substantia nigra. This brain area is responsible for movement control, and its malfunction leads to Parkinson’s motor symptoms. Despite increasing evidence implicating alpha-synuclein clumps in Parkinson’s development, anti-aggregation compounds have not been successful in clinical settings. Researchers from Johns Hopkins Medicine, Baltimore, Maryland, and Seoul National University, South Korea, developed carbon-based, graphene quantum dots (GQDs) to evaluate if these tiny particles can inhibit the formation and break up existing alpha-synuclein fibrils in the brain. In a laboratory dish, GQDs were able to stop the formation of new protein clumps and induce the disaggregation of mature fibrils. Discuss the latest research in the Parkinson’s News Today forums! Importantly, GQDs prevented neuronal death and loss of synapses (the junction between two nerve cells that allows them to communicate), reduced the formation of Lewy bodies, eased the dysfunction of mitochondria (cells’ energy power plants), and inhibited neuron-to-neuron transmission of alpha-synuclein fibrils. The team then assessed whether treatment with GQDs would ease Parkinson’s-related symptoms in mice injected with fibrils. They observed that GQDs were able to pass through the blood-brain barrier, prevented the loss of dopamine neurons, and improved motor function. Previous studies have discussed the potential use of GQDs to inhibit the formation of amyloid-beta fibrils in Alzheimer’s disease, which leads to the formation of senile plaques. “This might be a universal effect on any kind of fibrillation process related to disease,” Byung Hee Hong, PhD, one of the study’s authors, said in a NewScientist article. “It is expected that GQD-based drugs with appropriate modifications might provide a clue to support the development of new therapeutic agents for abnormal protein aggregation- related neurological disorders including Parkinson’s,” researchers wrote. However, Hong underscored the roadblocks still ahead before a GQD-based treatment may be available: “It’s hard to translate the results in mice to actual patients, whose systems are way more complicated. But we do believe quantum dots can make positive impacts to some extent,” he said.
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[Physics World] Graphene quantum dots could treat autoimmune disorders 28 May 2020 Quantum dots made from graphene could be used to treat the inflammatory bowel disease ulcerative colitis, a study in a mouse model has found. Graphene quantum dots (GQDs) effectively regulated the excessive immune response that is characteristic of ulcerative colitis, reducing intestinal inflammation and preventing tissue damage. This finding indicates that GQDs are promising therapeutic agents for the treatment of autoimmune disorders, the researchers say. At least 300,000 people in the UK have ulcerative colitis or Crohn’s disease – the two main forms of inflammatory bowel disease. These autoimmune diseases can cause inflammation, swelling and ulceration of the digestive system. Ulcerative colitis affects the rectum and colon, while Crohn’s disease can affect any part of the digestive system. There is no known cure for these life-long conditions. Patients can experience a range in severity of symptoms, with treatments including surgery and medication, such as immunosuppressants and biological therapies that target the immune system. But there are risks in taking these powerful drugs, particularly of catching serious and opportunistic infections, and developing cancers. Alternative therapeutics with less side effects are urgently needed. Kyung-Sun Kang, director of the Adult Stem Cell Research Center at Seoul National University in South Korea, explains that inflammatory bowel diseases are characterized by a “hyperimmune state”, with over-active macrophages and T cells. “T helper cells produce inflammatory cytokines in ulcerative colitis and you then have inflammation in the intestine,” he explains. There is previous evidence to suggest that GQDs have an impact on the immune system and now Kang and Byung Hee Hong, head of the Graphene Research Laboratory at Seoul National University, have found that they reduce intestinal inflammation in mice models of ulcerative colitis by suppressing excessive T cell activity. They also found that the GQDs switch the macrophages involved in the inflammatory response to a different type of macrophage that regulates the immune system. GQDs appear to “help maintain a homeostatic balance in the immune system”, Kang says. For their study, described in Science Advances, Kang, Hong and colleagues injected GQDs with an average size of 29 nm into the abdominal cavity of colitis model mice. GQD-treated mice had increased survival rates and reduced weight loss compared with untreated mice, and scored lower on a disease activity index based around weight loss, activity, stool consistency, bleeding and hair condition. They also had lower levels of a biomarker of ulcerative colitis and reduced shortening of the colon – a characteristic feature of the disease. When the team looked at levels of cytokines in the mice, they found marked reductions in interferon-γ, the major cytokine involved in inflammatory bowel disease, in mice treated with GQDs. These animals also had lower levels of other pro-inflammatory cytokines. The researchers conclude that the GQDs had preventive and therapeutic effects, and reduced disease severity. The exact mechanism behind the immune regulation is still unclear, but Hong tells Physics World that GQDs have very interesting properties that probably enable it to stabilize the immune system. This is likely to be due to their known powerful antioxidant effect and ability to scavenge reactive oxygen species, which helps reduce inflammation, and their random, non-universal structure that seems to stop them provoking an immune response. The GQDs showed negligible toxicity and were naturally cleared from the mice. “We increased the concentration up to 100 times more than the therapeutic condition, and all the mice survived,” Hong says. “In addition, we confirmed that GQDs are excreted through urine in a few weeks without accumulation in any organs.” The team is now looking to develop an oral version of the therapy and moving towards clinical trials. “After studying the pre-clinical research this year, we are targeting stage 1 clinical trials in 2022,” Hong tells Physics World. Michael Allen is a science writer based in the UK https://physicsworld.com/a/graphene-quantum-dots-could-treat-autoimmune-disorders/ https://advances.sciencemag.org/content/6/18/eaaz2630
2020-06-09
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Tiny Particles Prevent Neuronal Loss, Improve Motor Symptoms in Parkinson’s Mouse Study JULY 13, 2018 Jose Marques Lopes, PhD Tiny crystals known as quantum dots can block the formation of Parkinson’s hallmark protein clumps, lowering nerve cell death and motor deficits, a mouse study has found. The research, “Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease,” was published in Nature Nanotechnology. Quantum dots are very small, engineered crystals with a diameter of as few as 10 to 100 atoms. They have electronic and fluorescent properties that have been used in research. The particles are found in some TV screens, LED lights and solar cells. Because of their very small size, these particles, unlike most medicines, can bypass the blood-brain-barrier, a semipermeable membrane that protects the brain from outside circulation. Parkinson’s patients typically have protein deposits in their nerve cells, called Lewy bodies. There are protein clumps composed mainly of misfolded alpha-synuclein protein that form long strands, or fibrils, and lead to the progressive loss of dopamine-producing neurons in an area of the brain called substantia nigra. This brain area is responsible for movement control, and its malfunction leads to Parkinson’s motor symptoms. Despite increasing evidence implicating alpha-synuclein clumps in Parkinson’s development, anti-aggregation compounds have not been successful in clinical settings. Researchers from Johns Hopkins Medicine, Baltimore, Maryland, and Seoul National University, South Korea, developed carbon-based, graphene quantum dots (GQDs) to evaluate if these tiny particles can inhibit the formation and break up existing alpha-synuclein fibrils in the brain. In a laboratory dish, GQDs were able to stop the formation of new protein clumps and induce the disaggregation of mature fibrils. Discuss the latest research in the Parkinson’s News Today forums! Importantly, GQDs prevented neuronal death and loss of synapses (the junction between two nerve cells that allows them to communicate), reduced the formation of Lewy bodies, eased the dysfunction of mitochondria (cells’ energy power plants), and inhibited neuron-to-neuron transmission of alpha-synuclein fibrils. The team then assessed whether treatment with GQDs would ease Parkinson’s-related symptoms in mice injected with fibrils. They observed that GQDs were able to pass through the blood-brain barrier, prevented the loss of dopamine neurons, and improved motor function. Previous studies have discussed the potential use of GQDs to inhibit the formation of amyloid-beta fibrils in Alzheimer’s disease, which leads to the formation of senile plaques. “This might be a universal effect on any kind of fibrillation process related to disease,” Byung Hee Hong, PhD, one of the study’s authors, said in a NewScientist article. “It is expected that GQD-based drugs with appropriate modifications might provide a clue to support the development of new therapeutic agents for abnormal protein aggregation- related neurological disorders including Parkinson’s,” researchers wrote. However, Hong underscored the roadblocks still ahead before a GQD-based treatment may be available: “It’s hard to translate the results in mice to actual patients, whose systems are way more complicated. But we do believe quantum dots can make positive impacts to some extent,” he said.
2019-10-08
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[AlzForum] Nano-size Quantum Dots Bust Up Synuclein Pathology 13 Jul 2018 Best known to biologists as brightly glowing florescent tracers, quantum dots could also have therapeutic powers, says a new study. Work led by Han Seok Ko of Johns Hopkins University in Baltimore and Byung Hee Hong at the University of Seoul, South Korea, reveals that nano-scale carbon lattices bind to and dissolve α-synuclein fibers in vitro. In cells, the graphene quantum dots protect against α-synuclein toxicity, and prevent its spread between neurons. In animals, the dots protect neurons from the ravages of injected synuclein fibrils, or mutant synuclein expression, all without signs of toxicity. The findings are reported in the July 9 Nature Nanotechnology. Quantum dots made from graphene disaggregate α-synuclein fibers in vitro. In animals, the dots prevent α-synucleinopathy and improve motor function. Nanomaterials could provide new approaches to neuroprotection. “This exciting study presents a novel and very untraditional way of treating synucleinopathy,” said Poul Henning Jensen, Aarhus University in Denmark. “They have done a good job of documenting their observation of a protective effect, but understanding the mechanism will take more work,” he said. Quantum dots can be made of many materials—those derived from graphene (GQDs) consist of a single layer of carbon atoms arranged in a hexagonal lattice, sometimes with chemical modifications. GQDs look like small scraps of chicken wire, and are being developed as biosensors, imaging agents, and carriers for drug delivery. Interest in these nanostructures as therapeutic agents is on the rise. Some reports suggest they interfere with amyloid fiber formation, and disaggregate Aβ or α-synuclein fibrils (Mahmoudi et al., 2012; Li et al., 2014; Liu et al., 2015; Yang et al., 2015; Liu et al., 2018). Plane of Attack. In a molecular simulation, carboxyl groups (red) on a graphene quantum dot (gray lattice) bind to the amyloid core of α-synuclein fibril (tan), and unfold it via hydrophobic interactions. [Courtesy of Kim et al., 2018 Nature Nanotechnology.] In the new study, co-first authors Donghoon Kim and Je Min Yoo tested the ability of chemically modified GQDs to counteract the aggregation, transmission, and toxicity of α-synuclein. By treating pure carbon fibers with strong acid, the investigators generated 2 nm square snippets of graphene that sport carboxylic acid groups around their edges. When mixed in equal amounts with purified α-synuclein in vitro, these GQDs potently inhibited fibril formation. Even more, they rapidly dissolved preformed fibrils, first melting the structures into shorter fragments and then into monomers. Structural analysis with NMR and other techniques indicated that the GQDs’ negatively charged carboxyl groups bound to the positively charged N-terminal region of α-synuclein in fibrils. A molecular dynamics simulation predicted that hydrophobic interactions between valine residues in α-synuclein and the GQD lattice destroy the β-sheet structure, driving fibril dissociation (see image at right). In agreement with that idea, removing the carboxyl groups destroyed the GQDs’ fibril-busting activity. Moving to cell-based assays, the scientists demonstrated that GQDs protected primary cortical neurons from α-synuclein toxicity. The dots prevented cell death, restored neurite outgrowth and synaptic proteins, and mitigated mitochondrial toxicity induced by α-synuclein preformed fibrils (PFFs). Quantum dots also reduced the accumulation of phosphorylated and aggregated α-synuclein in response to PFFs, and blocked the transmission of α-synuclein pathology from cell to cell in vitro. Protection appeared to occur inside cells: In live imaging experiments, PFFs and GQDs were spotted together in lysosomes. There, the signal for PFFs decreased and that for GQDs increased over time, suggesting disaggregation of α-syn takes place in that compartment. The protective effects of GQDs extended to two different PD mouse models. In one, the researchers injected α-syn PFFs into the striata of wild-type mice. After 180 days, six mice lost about half of their dopamine neurons, whereas six animals also given GQD injections twice a week lost only about one-quarter. Treatment also reduced the spread of gliosis, pathologic phosphorylated α-synuclein, and Lewy body-like inclusions (see image below). The animals’ motor function improved too. GQD-treated mice had more control of their paws and balanced better on a pole. In a transgenic PD model, pathology and motor function improved when mice expressing A53T mutated human α-synuclein were treated with the GQDs. Nano Defense. In wild-type mice, the spread of α-synuclein fibrils caused by striatal injection of PFFs (top) is mitigated by GQDs (bottom). [Courtesy of Kim et al., 2018 Nature Nanotechnology.] The graphene dots even appeared safe. After four months of dosing, they caused no apparent harm to the mice. They were cleared in the urine. Multiple carboxyl groups packed onto teeny, inert scaffolds provide a potent, nontoxic, anti-aggregation agent, the authors concluded. How did GQDs get into the brain? The dots readily traversed layers of endothelial cells and astrocytes in an in vitro model of the blood-brain barrier. Fluorescent imaging showed both cell types accumulated GQDs in lysosomes and released them via exosomes. The scientists propose that GQDs are endocytosed by endothelial cells, then released via exosomes, to be taken up by astrocytes, and finally released into the brain. In vivo, the researchers detected GQDs widely in the central nervous system after intraperitoneal injection. Given studies suggesting they disassemble Aβ fibrils, these quantum dots might have applications beyond tackling synuclein fibrillogenesis. Ko told Alzforum they have confirmed that their GQDs can dissociate Aβ fibrils and oligomers in vitro. They are now testing the dots in a mouse model of AD, he said. At the same time, they are moving forward on the Parkinson’s disease front. Hong is working on safety studies in animals as a prelude to human use. “If all goes well we hope to start trials in people within two years,” Ko said. He believes GQDs will have a universal effect on neurodegenerative disorders that involve accumulation of fibrillar aggregates. “This paper opens a new research direction on chemical modified nanomaterial for anti-amyloid therapy,” wrote Mingdong Dong, Aarhus University, Denmark, in an email to Alzforum. Dong’s group is evaluating other nanomaterial as anti-amyloid agents (Wang et al., 2018). Jensen agreed, adding that he hopes the authors will clearly explain the procedure for making the dots. “I’m sure this paper will stimulate at lot of other studies. Their data suggest that it is important to produce the quantum dots in a specific way, and I hope they will describe the method in detail. If there is a trick to the production, it is important to document that,” he said. Jensen also told Alzforum he’d like to see more quantitation of the interaction between GQDs and fibrils, including measures of affinity and specificity for other amyloids, including nonpathogenic, physiological forms.—Pat McCaffrey
2019-10-08
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[Physics World] Could graphene quantum dots help treat Parkinson’s disease? Quantum dots made from the carbon material graphene prevent alpha-synuclein from aggregating into strand-like structures known as fibrils. They also help disaggregate fibrils that have already formed. Alpha-synuclein fibrils are thought to be implicated in Parkinson’s disease because they kill dopamine-generating neurons, so the new findings might help in the development of therapies to treat this disease as well as others in which fibrilization occurs. Synucleins are a family of proteins typically found in neural tissue. Researchers believe that one type of synuclein, alpha-synuclein, twists into fibrils, which then accumulate in the midbrain of patients with Parkinson’s. Treatments with efficient anti-aggregation agents might thus be one way of fighting the disease. A team led by Byung Hee Hong of Seoul National University and Han Seok Ko of The Johns Hopkins University in Baltimore have now found that graphene quantum dots (GQDs) bind to alpha-synuclein in vitro. Thanks to fluorescence and turbidity assays, as well as transmission electron microscopy measurements, the researchers found that the dots prevent alpha-synuclein from forming into fibrils. The nanostructures also dissociate already-formed fibrils into short fragments, with the average length of the fragments shortening from 1 micron to 235 nm and 70 nm after 6 and 24 hours respectively. The number of fragments starts to decrease after three days too and cannot be detected at all after seven days, which implies that the fibrils completely disintegrate after this time. Mice show improved symptoms of the disease after six months In their experiments, Hong and Ko’s team also injected the GQDs into the bloodstream of transgenic mice with Parkinson’s and found that they showed improved symptoms of the disease after six months – as assessed by routine cylinder and pole tests. The mice showed fewer movement problems, were able to use both forepaws to balance themselves on cylinders and ran down poles quicker. The researchers say that these improvements could come from the fact that the quantum dots are small enough to penetrate the blood-brain barrier and protect against dopamine neuron loss induced by alpha-synuclein preformed fibrils. The GQDs do not show any appreciable in vitro and in vivo toxicity after six months of “prolonged injection” either and can be cleared from the body and excreted into urine, they add. The quantum dots might produce a similar effect in other diseases in which fibrilization occurs. Indeed, previous research by another team has already shown that injecting them into mice with Alzheimer’s inhibits the fibrilization of beta-amyloid peptides. Full details of the research have been published in Nature Nanotechnology 10.1038/s41565-018-0179-y. Source: https://physicsworld.com/a/could-graphene-quantum-dots-help-treat-parkinsons-disease/
2019-10-08
About us
BIOGRAPHENE is a biotech startup dedicated to developing novel graphene-based nanomedicine for neurodegenerative diseases. With the headquarters (BioGraphene Inc.) and core R&D facilities located in Seoul, Republic of Korea, we are a spin-off company from Seoul National University and have been operating as a legal entity in the state of California starting in June 2020. BIOGRAPHENE is equipped with the technical prowess of Seoul National University’s researchers (Graphene Research Laboratory by Prof. Byung Hee Hong, Founder&CEO), as well as the integration of cutting-edge graphene synthesis and biomedical applications.
Our HistoryConnecting the Dots
2017Established BioGraphene Inc.
Seoul National University spin-off 1st paid-in capital increase
2014Major Patent Filed
Method-of-use patent of Graphene nanostructure for neurodegenerative diseases(Issued in Republic of Korea, Japan, Europe & United States)
2020Established US Branch
Located in Los Angeles, California, the US office focuses on the novel drug development for neurodegenerative diseases
2018Mass Production (In progress)
In collaboration with Graphene Square Inc. for the mass production of graphene quantum dots
Our LocationUS office located in Gas Company Tower, Downtown Los Angeles.
AddressBuild. B, 1st floor, 145, Gwanggyo-ro, Yeongtong-gu,
Suwon-si, Gyeonggi-do, Republic of Korea (HQ)
555 W 5th St. Los Angeles, CA (US branch)
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Meet BIOGRAPHENEEvents / Conferences (Gallery)