Glucosamine as a regulator of O-GlcNAc signaling: linking metabolism to disease pathogenesis

 

Have your competent? doctor reconcile the earlier research showing benefits! Sorry, no can do; YOUR DOCTOR WILL JUST PROVE THEIR INCOMPETENCE BY DOING NOTHING!

• glucosamine (6 posts to March 2015)

Glucosamine as a regulator of O-GlcNAc signaling: linking metabolism to disease pathogenesis

• Sang-Min Kim,
• Chanhaeng Lee,
• Dong Yeol Kim &
• Inn-Oc Han 

• 646 Accesses

• Explore all metrics

Abstract

Background

Glucosamine, a naturally occurring amino sugar abundant in cartilage, has long been utilized as a dietary supplement to alleviate osteoarthritis (OA) and joint pain. Beyond its structural role in maintaining joint integrity, glucosamine is metabolized through the hexosamine biosynthetic pathway (HBP) to generate UDP-N-acetylglucosamine (UDP-GlcNAc), the indispensable donor substrate for protein O-linked N-acetylglucosamine (O-GlcNAc) modification.

Findings

Accumulating evidence indicates that glucosamine-driven modulation of HBP flux and the consequent alteration of O-GlcNAcylation exert profound effects on cellular signaling, metabolic regulation, and inflammatory responses. These mechanisms extend far beyond musculoskeletal health, influencing the pathogenesis of diverse conditions such as rheumatoid arthritis (RA), diabetes, obesity, neuroinflammation, neurodegenerative disorders, sepsis, and cancer. Despite glucosamine’s long-standing clinical use, its potential role as a metabolic regulator of O-GlcNAc cycling remains underexplored.

Conclusion

This review integrates current insights into the molecular basis of glucosamine-enhanced O-GlcNAcylation, highlighting its implications for disease onset and progression, and proposing a broader therapeutic framework that positions glucosamine as a promising modulator of inflammation and systemic pathology.

Glucosamine Supplement Linked to Accelerated Alzheimer’s Progression

 Have your competent? doctor reconcile the earlier research showing benefits!

• glucosamine (5 posts to March 2015)

Glucosamine Supplement Linked to Accelerated Alzheimer’s Progression

Summary: A new study uncovered a highly provocative association between glucosamine, a massive over-the-counter joint supplement, and accelerated cognitive decline. The investigation combined artificial intelligence audits of 12 years of electronic health records with post-mortem human brain spatial assays and animal models.

The data reveals that glucosamine, which crosses the blood-brain barrier, fuels an already overactive protein “sugar-tagging” pathway in vulnerable brains. This metabolic dysregulation is associated with a 25% higher likelihood of progressing from Mild Cognitive Impairment (MCI) to Alzheimer’s disease, alongside a 25% increase in mortality risk for those with established dementia.

Key Facts

• The Joint Supplement Conundrum: Glucosamine is an exceptionally popular over-the-counter compound routinely taken by millions of seniors to mitigate arthritis and joint pain. Because it easily breaches the blood-brain barrier, it directly interacts with the central nervous system’s internal biochemistry.
• The 12-Year AI Record Audit: Collaborating investigators utilized artificial intelligence to systematically parse deidentified health records from UF Health spanning 2012 to 2024. The data revealed that an astonishing 8% of all monitored dementia and MCI patients were actively taking glucosamine supplements.
• The 25% Dementia Progression Spike: After rigorously controlling for baseline age, biological sex, and patient demographics, the retrospective analysis unmasked that glucosamine consumption is associated with a 25% higher probability of transitioning from mild cognitive impairment to full-blown dementia.
• Elevated Mortality in Established ADRD: For patients already living with Alzheimer’s Disease and Related Dementias (ADRD), taking glucosamine was linked to a 25% surge in short-term mortality risks. Interestingly, this mortality spike was absent in the MCI group, proving the Alzheimer’s brain is uniquely fragile to this metabolic stress.
• Overactive Sugar-Tagging Pathology: Using advanced spatial biomolecule technology, senior author Dr. Ramon Sun discovered that the Alzheimer’s brain suffers from an overactive protein sugar-tagging pathway. While healthy cells need precision sugar tags to fold proteins properly, the diseased brain adds too many sugar structures, gumming up cellular machinery.
• Animal and Post-Mortem Human Validation:
  • In Vivo Mice: Glucosamine directly accelerated protein sugar-tagging, severely degrading the animals’ social recognition memory. Chemically blocking this tagging process completely reversed the cognitive deficits.
  • Human Brain Bank: Post-mortem tissue samples from the UF Neuromedicine Brain and Tissue Bank verified heavily elevated sugar-tagging footprints in confirmed Alzheimer’s cases compared to healthy controls.
• Shifting Past Plaques and Tangles: This discovery firmly frames metabolic dysregulation as a primary, active driver of neurodegeneration rather than a passive, secondary symptom. It establishes a brand-new therapeutic target that complements existing medical strategies focused on amyloid-beta plaques and tau tangles.
• Source: University of Florida

New research has found an association between taking glucosamine, a popular over-the-counter supplement used for joint pain, and a higher likelihood of progressing from mild cognitive impairment to Alzheimer’s disease.

The finding by University of Florida neuroscientists is based on a large retrospective analysis of patients’ records as well as supporting data from advanced imaging technology used to scan human brain specimens and Alzheimer’s disease mouse models.

While the results are preliminary and require validation in a human clinical trial, they provide yet another piece of a much bigger mechanistic picture involving metabolic dysregulation and neurodegeneration, according to the study published today in Nature Metabolism.

Glucosamine supplements cross the blood-brain barrier and hyper-activate an underlying protein sugar-tagging metabolic defect, which is associated with a 25% accelerated progression from mild cognitive impairment to Alzheimer’s disease. Credit: Neuroscience News

“In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias such as Lewy body or frontotemporal dementia,” said senior author Ramon Sun, Ph.D., director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation of UF’s McKnight Brain Institute. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.”

As glucosamine is widely available and commonly used by seniors for joint health, researchers set out to investigate whether it could have any effect in Alzheimer’s disease and related dementias, known as ADRD.

With collaborators Yi Guo, Ph.D., and Jiang Bian, Ph.D., the team used artificial intelligence to comb deidentified UF Health records from 2012 to 2024 for patients diagnosed with either ADRD or mild cognitive impairment, or MCI. They found that a significant proportion — 8% — of both types of patients reported taking glucosamine: 1,896 with ADRD and 2,750 with MCI.

After controlling for age, sex and demographics, the analysis showed that glucosamine use was associated with a 25% higher likelihood of progression from mild cognitive impairment to dementia.

In addition, researchers found that taking glucosamine was associated with a 25% increase in mortality risk, or the likelihood of death within a specified time frame, among ADRD patients. For the MCI group, there was no such impact, suggesting the impact of glucosamine may be greater in patients with established dementia.

Notably, said Sun, researchers revealed that a metabolic process in which a protein and sugar-tagging pathway is overactive in Alzheimer’s could be a new target for intervention.

“Our results suggest that altered metabolism is a significant contributor to Alzheimer’s progression and, in addition, addressing the metabolic defect could be an important complement to approaches focused on Alzheimer’s plaques and tangles,” Sun said.

These new insights were made possible by powerful new spatial technology developed by Sun’s lab.

“This technology allows us to examine thousands and thousands of molecules created when the body breaks down food or drugs and to uncover intricate pathways that otherwise would stay hidden,” Sun said.

To peer more deeply into these pathways, the research team focused on glucosamine, a naturally occurring sugar-related molecule that can cross the blood-brain barrier and feed into pathways that build complex sugar structures on proteins. In supplements, it can be made from substances such as shellfish shells or corn.

The findings suggest that glucosamine’s impact may depend on biological context, with the Alzheimer’s brain appearing more vulnerable to this metabolic pathway than the nondiseased brain, said Matt Gentry, Ph.D., chair of UF’s Department of Biochemistry and Molecular Biology and a study co-author.

“The electronic health record data are very provocative,” Gentry said. “While it’s an association and not proof of causality, it does raise an important clinical question that now deserves much more attention.”

In genetically modified mice, the research team showed that glucosamine significantly increased the attachment of sugar residues to proteins in cells. Deficits in “social memory” — or memory of recognition — worsened in glucosamine-treated mice. Conversely, when researchers chemically suppressed this attachment process, memory improved.

Then, in collaboration with Stefan Prokop, M.D., the team found significantly increased sugar attachment in Alzheimer’s brain specimens from the UF Neuromedicine Brain and Tissue Bank compared with normal controls. Taken together, these results suggest that such metabolic dysfunction is not simply a secondary aspect of Alzheimer’s pathology but a contributing driver, they reported.

“Proteins are the cell’s molecular machines, and many of them need sugar tags added in just the right way to fold correctly, travel to the right place and do their jobs,” Gentry said.

“What we found in Alzheimer’s is that this sugar-tagging system appears to be overactive. The Alzheimer’s brain is adding too many of these sugar structures, and this seems to contribute to the disease rather than protect against it.”

Key Questions Answered:

Q: Does this study prove that taking glucosamine supplements directly causes Alzheimer’s disease?

A: No, it shows a strong statistical association, not absolute proof of cause and effect. The University of Florida researchers explicitly note that these findings are preliminary and must be validated in a formal human clinical trial. However, the data raises an urgent clinical warning because it aligns perfectly with the biological changes seen in human tissue and animal models.

Q: How can a common supplement meant for joint pain cause damage inside the human brain?

A: Because glucosamine can easily cross the blood-brain barrier. Once inside the brain, it acts as fuel for a specialized pathway that attaches sugar structures to proteins. While healthy brains use this pathway normally, the researchers discovered that an Alzheimer’s brain is highly defective and overactive, it adds way too many sugar structures, which disrupts how vital protein machines operate.

Q: I take glucosamine for my arthritis. Should I stop taking it immediately based on this study?

A: While this study is not an official medical directive, it does introduce vital data to discuss with your physician. If you have been diagnosed with mild cognitive impairment or have a family history of dementia, this research suggests the supplement might inadvertently accelerate brain cell stress. You should review your supplement list with your healthcare provider to weigh your joint health against your personal cognitive risk factors.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this Alzheimer’s disease research news

Author: Mickie Anderson
Source: UF Health
Contact: Mickie Anderson – UF Health
Image: The image is credited to Neuroscience News

Original Research: Open access.

“Hyperglycosylation is a metabolic driver of Alzheimer’s disease” by Tara R. Hawkinson, Zizhen Liu, Roberto A. Ribas, Terrymar Medina, Rikke S. Nielsen, Harrison A. Clarke, Xin Ma, Angela C. Mueller, Adrielle F. Plasencia, Alexander L. Sheer, Samantha T. Simpson, Charles M. Soto, Jessica Sudderth, Feng Cai, Alex R. Cantrell, Matthieu G. Colpaert, Cameron J. Shedlock, Lei Wu, Lyndsay E. A. Young, Damon D. Kooser, Li Chen, Alison M. Ryan, Sadi Quinones, Jihye Son, Parastoo Azadi, Ralph J. Deberardinis, Stefan Prokop, Derek Allison, Shuang Yang, Hongyu Chen, Yu Huang, Xing He, Kimberly M. Alonge, Jingchuan Guo, Yi Guo, Jiang Bian, Craig W. Vander Kooi, Matthew S. Gentry & Ramon C. Sun. Nature Metabolism
DOI:10.1038/s42255-026-01538-4

Popular Joint Supplement Tied to Faster AD Progression - Glucosamine

 

FYI. Ask your doctors what this means.  They have had 11 years to figure this out. How incompetent are they to have done nothing in 11 years?

• glucosamine (4 posts to March 2015)

• 
  

This research comes to a different conclusion than the latest one below so ask your doctor for EXACTNESS! Maybe age 60 is the cutoff point

The association between regular glucosamine use and risk of dementia

The latest here:

Popular Joint Supplement Tied to Faster AD Progression

Glucosamine, a popular joint-pain supplement, may worsen outcomes in people with mild cognitive impairment (MCI), and a newly identified metabolic pathway involving excessive protein glycosylation could help explain why, new research suggests.

In a large electronic health record analysis, glucosamine use was associated with a 25% higher likelihood of progression from MCI to dementia over 5 years. Experiments in human brain tissue and mouse models suggested that excessive protein glycosylation may contribute to Alzheimer’s disease (AD) progression and that glucosamine supplementation could exacerbate the process by fueling glycan production.

Although preliminary, researchers said the findings point to glycan metabolism as a possible therapeutic target and raise questions about the safety of glucosamine use among patients with established dementia.

“In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias such as Lewy body or frontotemporal dementia. A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse,” senior investigator Ramon Sun, PhD, director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation at the McKnight Brain Institute at the University of Florida, Gainesville, Florida, said in a statement.

Article Key Points

Glucosamine, a common joint supplement, may accelerate Alzheimer's progression by 25% over five years, potentially due to increased protein glycosylation. This raises concerns about its safety for dementia patients, warranting further investigation.

The study was published online on June 9 in Nature Metabolism.

The association between regular glucosamine use and risk of dementia

FYI. Ask your doctors what this means.  They have had 8 years to figure this out. How incompetent are they to have done nothing in 8 years?

• glucosamine (3 posts to March 2015)

   

The latest here:

The association between regular glucosamine use and risk of dementia

In a recent study published in the BMC Medicine Journal, researchers assessed the association between daily glucosamine consumption and the risk of new-onset dementia.

Study: Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study. Image Credit: Farion_O/Shutterstock.com

Background

The characteristic progressive cognitive impairments in dementia and lowered capacity to perform routine activities increase the health burden on the affected individuals and their health systems. Given the lack of effective pharmacological therapies for dementia, identifying modifiable factors with protective effects against dementia has garnered interest.

Glucosamine, an extensively used non-mineral, non-vitamin supplement for joint pain and osteoarthritis, reportedly has anti-neuroinflammatory and neuroprotective properties.

Of note, a study reported the relationship between glucosamine consumption and improved cognitive function, possibly due to its influence on energy metabolism and the involvement in the O-linked N-acetylglucosaminylation of proteins. However, data on the relationship between glucosamine consumption and the risk of dementia are limited.

About the study

In the prospective cohort study, researchers assessed any-cause dementia, vascular dementia, and Alzheimer's disease (AD) development risks in glucosamine consumers and non-consumers.

The study compared 55,794 United Kingdom (UK) Biobank participants, aged 40 to 70 years, with new-onset dementia data and no history of dementia. Individuals were recruited from 22 sites across the United Kingdom, including Scotland, Wales, and England, from 2006 to 2010.

For further testing of the causal relationship between glucosamine usage and dementia, a two-sample Mendelian randomization (MR) analysis was performed utilizing genome-wide association study (GWAS) summary-level data. In addition, the team explored the probable modifying effects of various known risk factors, including the apolipoprotein E (APOE ε4) genotypes for dementia.

Cox proportional hazard-type modeling was performed, and the hazard ratios (HR) were calculated. Data were adjusted for age, sex, level of education, ethnicity, education, income, Townsend deprivation index (TDI), body mass index (BMI), fruit and vegetable consumption, smoking habits, alcohol consumption, physical activity, comorbidities, medications, and dietary supplements. Comorbidities were assessed using the Elixhauser comorbidity index.

Data were analyzed via digital questionnaires, physical evaluation, in-person interviews, and hospitalization and death records. The team obtained genome-wide association studies' data from observational cohorts comprising primarily Europeans. Diagnoses were based on the international classification of diseases, tenth revision (ICD-10) codes.

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Digital assessments and pair-matching tests were performed to assess memory and reaction time. The team excluded 1,298 individuals who withdrew from the study, 224 individuals with prior dementia history, 6,171 individuals with missing data on glucosamine usage, and 15,339 lacking genotyping data.

Results and discussion

In total, 494,814 individuals were considered for the final analysis, among whom the mean participant age was 57 years, 54% were women, and 19% (n=94,259) of participants documented glucosamine usage at baseline.

During the nine-year follow-up (median) period, 2,458, 924, and 491 cases of any-cause dementia, AD, and vascular dementia, respectively, were reported. The HR values for glucosamine consumers for any-cause dementia, vascular dementia, and AD were 0.8, 0.7, and 0.0, respectively.

The positive but inverse association between the use of glucosamine and Alzheimer's disease was stronger among participants aged <60 years compared to individuals aged >60 years, and the associations were not modified by the apolipoprotein E genotype.

Single-variable Mendelian randomization analysis findings indicated a causal association between glucosamine use and a lower risk of dementia. Multivariable Mendelian randomization analysis findings showed that glucosamine use prevented dementia after data were controlled for vitamin and/or chondroitin supplementation and osteoarthritis, with HR values for any-cause dementia, vascular dementia, and AD being 0.9, 0.7, and 0.8, respectively.

The single variable analysis, multivariable inverse variance weighted (MV-IVW), and sensitivity analysis yielded similar findings. Excluding individuals reporting outcomes within two years of follow-up, individuals using chondroitin, and those with missing data, the association between glucosamine usage and any-cause dementia, vascular dementia, and AD persisted.

In the follow-up period, among individuals without dementia, 19,763, 19,654, and 19,082 deaths were reported as competing events for vascular dementia, AD, and all-cause dementia, respectively. The competing risks analysis findings were consistent with Cox proportional hazard-type modeling.

Passing through the blood-brain barrier (BBB), glucosamine may enter the hippocampus, cortex, and striatum. The stronger influence of glucosamine on AD patients aged <60 years, compared to the elderly, may be related to the gradually progressing hippocampal atrophy and lowering of cortical density with advancing age, decreasing the number of brain cell membrane receptors, and lowered sensitivity to medications.

Glucosamine may simulate low-carbohydrate diets by reducing glycolysis, increasing the catabolism of amino acids, and may reverse intestinal microbial dysbiosis.

Conclusions

Overall, the study findings provide evidence for potential causal relationships between glucosamine usage and a lower risk for dementia. Daily glucosamine usage was associated with a 15.0% lower risk of any-cause dementia, 17.0% for Alzheimer's disease, and 26.0% for vascular dementia. The APOE genotype did not modify the association.

Glucosamine use was associated with improved cognitive functions, with a higher reasoning score and faster reaction speed among glucosamine users compared to non-users. Glucosamine may also prevent dementia, irrespective of chondroitin supplementation. Randomized controlled trials (RCTs) must be conducted in the future to validate the study findings.

Journal reference:

• Zheng, J. et al. (2023) "Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study", BMC Medicine, 21(1). doi: 10.1186/s12916-023-02816-8. https://https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02816-8

Glucosamine supplements may be linked to lower risk of cardiovascular disease

Why should I trust anything you say here when you don't know that the WHO reclassified stroke in 2006, now a neurological disease not cardiovascular disease.

But useless, since amounts are not given. 

Glucosamine supplements may be linked to lower risk of cardiovascular disease

Findings suggest possible preventive role, but further trials needed to test this theory

Regular use of glucosamine supplements may be related to a lower risk of cardiovascular disease (CVD) events, suggests an analysis of data from the UK Biobank study, published in The BMJ today.
The findings suggest that glucosamine may have benefits in preventing CVD events, such as coronary heart disease and stroke, and further clinical trials are needed to test this theory, say the researchers.
Glucosamine is a popular dietary supplement used to relieve osteoarthritis and joint pain. While its effectiveness on joint pain continues to be debated, emerging evidence suggests that glucosamine may have a role in preventing cardiovascular disease and reducing mortality. However, conclusive evidence is still lacking
So to explore these potential associations further, researchers led by Professor Lu Qi at Tulane University in New Orleans drew on data from the UK Biobank - a large population based study of more than half a million British men and women.
Their analysis included 466,039 participants without CVD, who completed a questionnaire on supplement use, including glucosamine.
Death certificates and hospital records were then used to monitor CVD events, including CVD death, coronary heart disease (CHD), and stroke, over an average seven-year follow up period.
Overall, almost one in five (19.3%) participants reported glucosamine use at the start of the study.
The researchers found that glucosamine use was associated with a 15% lower risk of total CVD events, and a 9% to 22% lower risk of CHD, stroke, and CVD death compared with no use.
These favourable associations remained after taking account of traditional risk factors, including age, sex, weight (BMI), ethnicity, lifestyle, diet, medication and other supplement use.
The association between glucosamine use and CHD was also stronger in current smokers (37% lower risk) compared with never (12%) and former smokers (18%).
Several mechanisms may explain these results, say the authors. For example, regular use of glucosamine has been linked to a reduction in levels of C-reactive protein (CRP), a chemical associated with inflammation. This may also help to explain the stronger association among smokers, who have higher levels of inflammation and higher risk of CVD than non-smokers.
In addition, previous data suggest that glucosamine may mimic a low carbohydrate diet, which has been inversely associated with the development of CVD.
Despite the large sample size, this is an observational study, and as such, can’t establish cause, and the researchers point to some limitations, such as lack of information on dose, duration, and side effects of glucosamine use.
Regular glucosamine use may also be a marker for a healthy lifestyle, they add, but this is unlikely to have affected the results.
As such, they conclude that “habitual use of glucosamine supplements to relieve osteoarthritis pain might also be related to lower risks of CVD events. Further clinical trials are warranted to test this hypothesis.”
[Ends]

14/05/2019

Notes to Editors
Research: Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank
Journal: The BMJ
Link to Academy of Medical Sciences press release labelling system: https://press.psprings.co.uk/AMSlabels.pdf

Peer-reviewed? Yes
Evidence type: Observational
Subjects: People
Link to research: https://www.bmj.com/content/365/bmj.l1628

A dietary supplement dampens the brain hyperexcitability seen in seizures or epilepsy

You'll have to bring this to your doctors attention if you are in this cohort; seizures occur in about 10% of stroke patients. 
Or maybe you want this:

Cannabidiol May Reduce Seizures by Half in Hard-to-treat Epilepsy

Or maybe the nasal spray referred to in here:

Preventing Seizure-Caused Damage to the Brain

The answers are out there, does your doctor know about them?

 

A dietary supplement dampens the brain hyperexcitability seen in seizures or epilepsy 

Seizure disorders—including epilepsy—are associated with pathological hyperexcitability in brain neurons. Unfortunately, there are limited available treatments that can prevent this hyperexcitability. However, University of Alabama at Birmingham researchers have found that inducing a biochemical alteration in brain proteins via the dietary supplement glucosamine was able to rapidly dampen that pathological hyperexcitability in rat and mouse models.

These results represent a potentially novel therapeutic target for the treatment of seizure disorders, and they show the need to better understand the physiology underlying these neural and brain circuit changes.
Proteins are the workhorses of living cells, and their activities are tightly and rapidly regulated in responses to changing conditions. Adding or removing a phosphoryl group to proteins is a well-known regulator for many proteins, and it is estimated that human proteins may have as many as 230,000 sites for phosphorylation.
A lesser-known regulation comes from the addition or removal of N-acetylglucosamine to proteins, which is usually controlled by glucose, the primary fuel for neurons. Several years ago, neuroscientist Lori McMahon, Ph.D., professor of cell, developmental and integrative biology at UAB, found out from her colleague John Chatham, D.Phil., a UAB professor of pathology and a cardiac physiologist, that brain cells had the second-highest amounts of proteins with N-acetylglucosamine, or O-GlcNAcylation, in the body.
At the time, very little was known about how O-GlcNAcylation might affect brain function, so McMahon and Chatham started working together. In 2014, McMahon and Chatham, in a study led by graduate student Erica Taylor and colleagues, reported that acute increases in protein O-GlcNAcylation caused long-term synaptic depression, a reduction in neuronal synaptic strength, in the hippocampus of the brain. This was the first time acute changes in O-GlcNAcylation of neuronal proteins were shown to directly change synaptic function.
Since neural excitability in the hippocampus is a key feature of seizures and epilepsy, they hypothesized that acutely increasing protein O-GlcNAcylation might dampen the pathological hyperexcitability associated with these brain disorders.
That turned out to be the case, as reported in the Journal of Neuroscience study, "Acute increases in protein O-GlcNAcylation dampen epileptiform activity in hippocampus." The study was led by corresponding author McMahon and first author Luke Stewart, a doctoral student in the Neuroscience Theme of the Graduate Biomedical Sciences Program. Stewart is co-mentored by McMahon and Chatham.

"Our findings support the conclusion that protein O-GlcNAcylation is a regulator of neuronal excitability, and it represents a promising target for further research on seizure disorder therapeutics," they wrote in their research significance statement. The researchers caution that the mechanism underlying the dampening is likely to be complex.
Research details
Glucose, the major fuel for neurons, also controls the levels of protein O-GlcNAcylation on proteins. However, high levels of the dietary supplement glucosamine, or an inhibitor of the enzyme that removes O-GlcNAcylation, leads to rapid increases in O-GlcNAc levels.
In experiments with hippocampal brain slices treated to induce a stable and ongoing hyperexcitability, UAB researchers found that an acute increase in protein O-GlcNAcylation significantly decreased the sudden bursts of electrical activity known as epileptiform activity in area CA1 of the hippocampus. An increased protein O-GlcNAcylation in normal cells also protected against a later induction of drug-induced hyperexcitability.
The effects were seen in slices treated with both glucosamine and an inhibitor of the enzyme that removes O-GlcNAc groups. They also found that treatment with glucosamine alone for as short a time as 10 minutes was able to dampen ongoing drug-induced hyperexcitability.
In common with the long-term synaptic depression provoked by increased O-GlcNAcylation, the dampening of hyperexcitability required the GluA2 subunit of the AMPA receptor, which is a glutamate-gated ion channel responsible for fast synaptic transmission in the brain. This finding suggested a conserved mechanism for the two changes provoked by increased O-GlcNAcylation—synaptic depression and dampening of hyperexcitability.
The researchers also found that the spontaneous firing of pyramidal neurons in another region of hippocampus, area CA3, was reduced by increased O-GlcNAcylation in normal brain slices and in slices with drug-induced hyperexcitability. This reduction in spontaneous firing of CA3 pyramidal neurons likely contributes to decreased hyperexcitability in area CA1 since the CA3 neurons directly excite those in CA1.
Similar to the findings for brain slices, mice that were treated to increase O-GlcNAcylation before getting drug-induced hyperexcitability had fewer of the brain activity spikes associated with epilepsy that are called interictal spikes. Several drug-induced hyperexcitable mice had convulsive seizures during the experiments—this occurred in both the increased O-GlcNAcylation mice and the control mice. Brain activity during the seizures differed between these two groups: The peak power of the brain activity for the mice with increased O-GlcNAcylation occurred at a lower frequency, as compared with the control mice.

Explore further: The molecular mechanisms of Alzheimer's

More information: Luke T. Stewart et al, Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus, The Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.0173-16.2017

Journal reference: Journal of Neuroscience
Provided by: University of Alabama at Birmingham

 

Sweet nanoparticles target stroke

Since we don't have a stroke organization in charge to update and run the stroke strategy this new idea will fall thru the cracks.   You could talk to the ASA, NSA, WSO but that will be worthless.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=150657&CultureCode=en
Materials resulting from chemical bonding of glucosamine, a type of sugar, with fullerenes, kind of nanoparticles known as buckyballs, might help to reduce cell damage and inflammation occurring after stroke. A team from the Max Planck Institute in Germany has tested this on mice, opening the door to potential new drugs for the cerebrovascular accident.

The majority of stroke occurs when the blood vessels that reach the brain are blocked by clots or fatty deposits which decrease the flow of blood towards its cells. It is then that an ischemic attack occurs, a pathology that leads to the degeneration of neurones, which can be fatal and not many drugs can treat.

Now, German and Swiss scientists have discovered that the combination of two substances help to reduce inflammation and the brain volume affected after a cerebrovascular accident. This is glucosamine, an amino sugar commonly used to treat arthritis and arthrosis; and certain derivatives of fullerenes, hollow and spherical structures formed by many carbon atoms.

Before now it was known that the fullerenes capture chemical radicals well which makes them act as neuroprotective agents, while the glucosamine brings down the inflammation.

What the researchers have done is chemically bond the two compounds to produce what is known as 'glyconanoparticles'. These have subsequently been administered to laboratory rats which then had a cerebrovascular accident induced.

The results, published in the journal 'Experimental Neurology', conclude that this combination of fullerene derivatives and glucosamine reduces cell damage and inflammation after a stroke, according to the MRI scans of animal brains and the improvement of their neurological symptoms.

"Our study confirms that it is possible to couple fullerenes with sugars in order to combine their protective effects and in this way, to obtain new materials which may help to prevent and to treat Stroke," says Guillermo Orts-Gil, a Spanish researcher at the Max-Planck Institute of Colloids and Interfaces (Germany) and co-author of the research.

"Although the present study was carried out on mice, the results indicate that these sweet buckyballs are potential new drugs for treating Stroke also in humans. However, this must be taken with caution, since what works in mice does not necessarily will work in the same way in humans," declared Orts-Gil.

This work is the continuation of another previous piece of research, published last year in the journal 'Nano Letters', in which the researchers also confirmed that a protein called E-selectin, linked to the chain of events that occur during a stroke, is distributed throughout the brain and not only in the area where the stroke originates, as previously thought.