Strategies to enhance proteostasis in the brain

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

A new study by Jose A. Rodriguez, et al, "identifies a novel strategy for preventing unwanted proteins from clogging synapses and ultimately congealing into protein plaques." "The findings demonstrate that boosting levels of the protein PI31 can prevent neuronal degeneration, restore synaptic function, and significantly extend lifespan in fly and mouse models of rare genetic disorders similar to #ParkinsonsDisease. These results may also hold promise for treating #AlzheimersDisease and slowing age-related cognitive decline." “A number of diseases, #Alzheimers, #Parkinsons, are in fact diseases of synaptic dysfunction, at least initially... Now that we’ve shown how to eliminate unwanted proteins at the synapse, we hope this will lead to a revolution in treating common age-related disorders.” - Hermann Steller, head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller. Learn More in PNAS https://lnkd.in/eT9Y__z4 PI31 expression is neuroprotective in a mouse model of early-onset parkinsonism - José A. Rodríguez, Adi Minis, PhD, Rasha Aref, Hoang Minh Hieu N. Nguyen, Fiona Sun, and Hermann Steller Strang Laboratory of Apoptosis and Cancer Biology, The Rockefeller University Overview by The Rockefeller University  https://lnkd.in/e8XBT8Pm

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