Neurodegenerative Disease Research

Changing the paradigm in Multiple Sclerosis therapeutics: from immuno-therapy to reducing glutamate excitotoxicity. Current MS research focuses on the autoimmune response causing demyelination, but evidence suggests neurodegeneration may come first. Glutamate receptor antagonists offer promise, but they also block essential neuronal functions. In this study, researchers used an AI screening to identify a small molecule that prevents excitotoxicity by targeting an allosteric binding site on the GluA2 subunit of the AMPA receptor. In MS animal models, this molecule restores neurological function and myelination, reduces the immune response, and avoids common off-target effects of glutamate antagonists. These results suggest a new treatment approach for MS with a different mechanism of action, potentially offering an alternative or complementary therapy to existing medications. The original article was published in Science Advances: https://lnkd.in/eePdxfdE. https://lnkd.in/eHQsXW9h #genetics #genomics #precisionmedicine #genomicmedicine #multiplesclerosis #brain #neurology #neurodegeneration #neuroscience #therapeutics #drugdiscovery #pharmacology #ai #machinelearning #immunology #immunity #neuroinflammation #biotechnology #innovation #research #science #sciencecommunication

🚀 Exciting Breakthrough in Progressive MS Research! 🚀 My team at the University of Cambridge, in collaboration with Isabel Beerman at the National Institute on Aging (and many other friends), has uncovered a potentially ground-breaking discovery in the fight against #progressivemultiplesclerosis (MS). This work was spearheaded by Alexandra Nicaise, a key member of my team at Cambridge and co-lead author, along with Irina Mohorianu, co-senior author, also based at Cambridge. Using a pioneering ‘disease in a dish’ model, we identified a novel brain cell type—disease-associated radial glia-like cells (DARGs). These cells originate from mature astroglia undergoing adaptive developmental reprogramming and appear to play a central role in driving #chronicinflammation and #neurodegeneration in progressive MS. Notably, DARGs revert to an early developmental stage and exhibit features of premature #aging, actively contributing to the damaging environment within the brain. This discovery opens new avenues for targeted therapies that could transform treatment for this devastating disease, offering hope to thousands. Our findings may also provide insights into other neurodegenerative conditions. Stay tuned as we delve deeper into the molecular machinery of #DARGs and explore their potential as therapeutic targets! With Alexandra Nicaise Irina Mohorianu Lukas Valihrach Pranathi Prasad Luca Peruzzotti Jametti Gabriel Balmus #MSResearch #Neuroscience #MedicalInnovation #Breakthrough #Neurodegeneration https://lnkd.in/esqJWjfP

In a major step toward understanding multiple sclerosis (MS), researchers have pinpointed two specific strains of gut bacteria that may play a key role in triggering the disease. The study, led by a team from Ludwig Maximilian University of Munich, focused on 81 pairs of identical twins where one sibling had MS and the other did not. This design allowed scientists to control for genetic and many environmental variables, honing in on the differences in gut microbiomes. The culprits? Two strains—Eisenbergiella tayi and Lachnoclostridium—were significantly more common in those with MS and, when transferred to mice, appeared to contribute to MS-like disease. Though previous studies have hinted at a link between gut bacteria and MS, this is the most precise identification to date. While more research is needed, especially in humans, the findings support the growing theory that the gut-brain connection plays a role in autoimmune diseases like MS. Understanding how these bacteria influence immune responses could eventually lead to targeted treatments that prevent or slow disease progression by modifying the microbiome. The research opens new doors to how we might one day tackle MS—starting in the gut. read the paper https://lnkd.in/dh-gy9sz

Exciting Advances in Multiple Sclerosis Research: Long-term Patient-reported Outcomes 🎉📊 I'm thrilled to share our recent publication in Brain Communications, "Patient-reported outcomes in multiple sclerosis: a prospective registry cohort study." Alongside an incredible team, we've explored the power of patient-reported outcomes (PROs) to monitor and predict the progression of multiple sclerosis (MS). This study analysed data from the United Kingdom Multiple Sclerosis Register, encompassing 15,976 MS patients over 11 years. Key findings include: Validation of PROs: Demonstrated as reliable measures of physical disability, sensitive to disease subtype and duration. ✅ Early Detection: Higher PRO scores in the relapsing-remitting phase can predict future transition to progressive forms. 🔍 Cost-effective Monitoring: PROs enable long-term, home-based monitoring, offering a patient-centric approach. 🏠 Unique aspects of this study include the use of a novel Monte Carlo permutation-based statistical method to handle sparse data and the comprehensive analysis of over 91,000 records. These findings underscore the potential of PROs in enhancing MS management and supporting early intervention strategies. A huge thank you to MS Register UK https://ukmsregister.org/, leading authors and MS patients involved! 🙌 For more details, check out the full article below. #MultipleSclerosis #MSResearch #PatientOutcomes #Neurology #HealthcareInnovation #MSregister #NHS #UK https://lnkd.in/e-uMTQgF

🧠Pushing the Boundaries of MS Imaging: Our Latest Research in MS Featured in #JMRI Multiple sclerosis (MS) is a complex autoimmune neuroinflammatory disease that affects millions worldwide, challenging clinicians with its heterogeneous presentation and progression. Traditional MRI has long been the cornerstone for diagnosing and tracking MS, yet it has limitations in detecting subtle changes and differentiating clinical subtypes. In our latest comprehensive review, we explore advanced MRI methods that are transforming the landscape of MS imaging. Techniques such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), quantitative susceptibility mapping (QSM), susceptibility-weighted imaging (SWI), and many others offer unprecedented insights into demyelination, lesion progression, and neurodegeneration in both white and gray matter. Our work highlights: ✅ Novel biomarkers grounded in MS pathophysiology ✅ Enhanced sensitivity and specificity beyond conventional MRI ✅ Potential to monitor disease progression across MS stages ✅ A proposed imaging protocol integrating these cutting-edge techniques 📈This review is a step forward in precision imaging for MS, paving the way for improved patient management and personalized therapeutic strategies. 📄 You can find the paper at the link below: https://lnkd.in/esesZekq 📬 For collaboration or inquiries, contact ✉️ Hamidreza Saligheh Rad, PhD, DBA (hamid.saligheh@gmail.com) ✉️ mohammad ali sahraian (sahraian1350@yahoo.com) #MultipleSclerosis #MRI #Neuroimaging #MedicalResearch #Neuroscience #AdvancedImaging #PrecisionMedicine #MSResearch #JMRI

Researchers now hope to launch human clinical trials in their quest for an Alzheimer’s vaccine to prevent the buildup of tau protein. A new study found that the experimental vaccine generated a robust immune response in both mice and non-human primates, building on earlier research. The researchers also tested antibodies in the serum from the immunized monkeys on samples of blood plasma drawn from people with mild cognitive impairment, often a precursor to full-blown Alzheimer’s dementia, as well as the sera in brain tissue from people who had died from Alzheimer’s, and found that they bound to the human version of the tau protein. Source in comments.

Scientists have discovered a naturally occurring protein inside our cells that could become a game-changer in the fight against aging and neurodegenerative diseases. Known as Protein Disulfide Isomerase, or PDI, this protein works like a microscopic repair crew, fixing broken DNA and protecting brain cells from conditions such as Alzheimer’s, Parkinson’s, and motor neuron disease. PDI is normally involved in organising proteins inside the cell, ensuring they fold correctly and function properly. Recent research has shown that PDI can also enter the nucleus, the part of the cell where DNA is stored, and repair tiny breaks caused by everyday damage, including UV light and pollution. These small but cumulative DNA damages contribute to the decline in cell function as we age. Strengthening this repair system could help maintain brain health for longer. Neurons in the brain are particularly vulnerable because they do not regenerate like other cells. Over time, accumulated DNA damage leads to cell death, memory loss, and movement difficulties. Experiments have demonstrated that cells without PDI cannot repair DNA effectively, but when PDI is introduced, their repair systems are restored. In zebrafish, increasing PDI levels helped protect them from aging-related DNA damage, showing the protein’s potential beyond just human cells. The implications of this discovery are vast. By harnessing PDI’s repair capabilities, researchers hope to develop therapies that slow or even prevent the onset of neurodegenerative diseases. Gene therapies, including mRNA-based approaches, are being explored to boost PDI activity in the brain, potentially offering a way to maintain cognitive and motor function as we age. Interestingly, PDI also plays a role in protecting cancer cells, which means that controlling its activity precisely will be essential for therapeutic applications. Understanding how to balance PDI’s protective benefits for healthy cells while limiting its support of cancer cells could unlock treatments for both brain aging and certain cancers. This breakthrough shines a light on the intricate systems within our cells that protect us from aging and disease, showing how cutting-edge research can transform our understanding of health and longevity. PDI represents not just a protein, but a promising path toward healthier brains and longer, more active lives. Follow Minds Canvas to stay updated on groundbreaking discoveries shaping the future of science and medicine. #DNARepair #BrainHealth #ProteinDisulfideIsomerase #PDI #NeurodegenerativeDiseases #AntiAging #GeneTherapy #ScientificDiscovery #Longevity #MindsCanvas

Remyelination therapy for multiple sclerosis may be a step nearer. Over a decade ago, the Chan lab discovered that antimuscarinic compounds promote the generation of myelinating oligodendrocytes (OL) that are capable of supporting the concentric wrapping of axon-like structures. In 2017, Dr. Ari Green published the first successful clinical trial of a remyelinating agent, finding that clemastine improved visual evoked potentials in MS patients with optic neuropathy. This new publication from the Chan lab describes research leading to the identification of PIPE-307, a compound that functions as an antagonist of M1R receptors, which are expressed on oligodendrocyte precursors (OLPs). This antagonism of M1R on OLPs stimulates their differentiation into myelinating OLs. PIPE-307-mediated generation of myelinating OLs stimulates the remyelination of axons and the restoration of neuronal function. This could lead to a clinical breakthrough, subject to all the usual caveats. And it's fascinating to see the involvement of the M1 muscarinic receptor - my first publication (1982) was of studies of presynaptic muscarinic inhibition in the electric organ of Torpedo marmorata in which wein directly discovered that there was a subclassification of the previously understood "muscarinic receptor" (life seemed easier when there was only one). https://lnkd.in/dQUhu7rc

Taming Prion Diseases Naturally: INP-Driven Discovery of 30 Phytocompounds Prion diseases—like CJD, variant CJD, Kuru, Fatal Familial Insomnia, and GSS—are caused by misfolded proteins (PrP^Sc) that induce normal proteins (PrP^C) to misfold, forming amyloid fibrils, triggering neuronal death, oxidative stress, ER stress, and inflammation. Long incubation periods and cross-species transmission make future outbreaks a serious threat. Using our INP 10-layer module, we identified 30 phytocompounds that inhibit prion misfolding and propagation: Future Threats: Potential emergence of novel prion strains through cross-species transmission. Difficulty in diagnosis and lack of FDA-approved treatments. Risk of iatrogenic transmission via surgical instruments or biological products. Long incubation periods → silent spread in populations. Top Phytochemicals & Mechanisms: Curcumin, Resveratrol, EGCG, Quercetin, Apigenin, Kaempferol, Luteolin, Fisetin, Myricetin, Genistein, Withaferin A, Berberine, Silymarin, Tetrahydrocurcumin, Baicalein, Carnosic acid, Rosmarinic acid, Thymoquinone, Ellagic acid, Chlorogenic acid, Pterostilbene, Mangiferin, Beta-caryophyllene, Andrographolide, Schisandrin B, Hesperetin, Gallocatechin, Curcumin derivatives, Ursolic acid, Oleanolic acid. Mechanistic Insights (INP Layer Analysis): Direct PrP^Sc binding → prevents misfolding & fibril formation Proteostasis enhancement → autophagy & proteasomal degradation Antioxidant activity → reduces ROS-induced toxicity ER & mitochondrial stress modulation → prevents apoptosis Anti-inflammatory pathways → limits glial activation & neuroinflammation Impact: Inhibits prion propagation → neuroprotection Safe, plant-derived modulators → potential therapeutics Opens pathways for precision phytopharmacology in protein-misfolding diseases #PrionDiseases #INPModule #Phytochemistry #Neuroprotection #Curcumin #Resveratrol #EGCG #Quercetin #WithaferinA #Berberine #NextGenNeurotherapeutics #ProteinMisfolding #AmyloidInhibition #PrecisionPhytopharmacology #Neurodegeneration #NaturalBioactives