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The Hindu
12-07-2025
- Health
- The Hindu
When cells rush to repair DNA, they also know when to stop
When ultraviolet light, certain chemical compounds or even normal copying mistakes harm our DNA, cells rush to fix the damage. Doing so means making the right repair proteins — but also not too many. Using baker's yeast and human skin cells, a new study has shown that cells temporarily slow the step in which protein-building machines read messenger RNA, or mRNA, for specific repair genes. In this process, two guardian proteins act like traffic lights that turn those messages from green to red until the emergency has passed. The work uncovers a previously hidden layer of the DNA damage response that prevents both dangerous under-repair and wasteful over-repair. 'It is a smart, evolutionarily conserved strategy that helps cells survive,' Indian Institute of Science associate professor and the study's lead investigator Purusharth I. Rajyaguru said. The study, together with researchers at Institut Curie, Paris, was published recently in EMBO Reports. The researchers attached green fluorescent tags to two proteins, Scd6 (yeast) or LSM14A (humans), and filmed living cells. When the team damaged DNA by treating it with hydroxyurea, the tagged proteins condensed into bright dots called RNA granules. Further analysis revealed that the hydroxyurea made Scd6 clump together while removing the stress dissolved the clumps. This indicated the holding areas were reversible rather than the cell's trash bins. Inside those granules, the researchers found that Scd6 captured the mRNA for an enzyme called Srs2, which unwinds DNA. This action caused the cells to produce lower quantities of Srs2. The researchers confirmed this by mutating either of Scd6's two RNA-gripping regions and found that it couldn't capture the mRNA to make Srs2. Yeast lacking in the Scd6 protein grew poorly when extra Srs2 was present inside cells when the DNA was treated with hydroxyurea, proving that reducing Srs2 production could actually protect the cell. The team found a similar process in human cells. The LSM14A protein also formed granules after hydroxyurea treatment. When LSM14A production was knocked down, the cell made more of two enzymes called RTEL1 and LIG4 that encouraged the cells to stitch broken DNA ends together in an error-prone way. 'Interfering with RNA granule dynamics might be a way to disrupt stress adaptation in cancer cells, making them more vulnerable to chemotherapy,' Dr. Rajyaguru said. 'We are also addressing this aspect in the context of neurodegeneration in our laboratory.'
Globe and Mail
21-02-2025
- Health
- Globe and Mail
Ibogaine by David Dardashti Explores Groundbreaking Research Linking Genetic Enhancers to Neurological Disease Treatment, Including Parkinson's
Ibogaine by David Dardashti, a leading voice in the exploration of ibogaine's therapeutic potential, is closely analyzing a new study published in EMBO Reports that sheds light on the intricate genetic mechanisms underlying neurological disorders, including Parkinson's disease. This research, spearheaded by Associate Professor Masahito Yoshihara and colleagues, provides compelling evidence that could significantly impact the understanding and application of ibogaine treatment. The study utilized advanced genomic techniques, including CAGE, NET-CAGE, and Capture Hi-C/HiCap, to identify and characterize thousands of enhancers – non-coding DNA regions that play a crucial role in gene regulation – active during neuronal differentiation. Crucially, the researchers discovered a significant enrichment of genetic variants (SNPs) associated with Parkinson's disease and schizophrenia within these enhancers. This finding suggests that these enhancers, and the genes they regulate, are directly implicated in the development and progression of these conditions. David Dardashti, a prominent advocate for ibogaine research, recognizes the profound implications of this study for the field of ibogaine therapy. "This research provides a critical piece of the puzzle in understanding how ibogaine may exert its remarkable effects," Dardashti explains. "By demonstrating the direct involvement of specific genetic enhancers in neurological disorders, it opens up exciting new avenues for exploring ibogaine's mechanism of action at a molecular level." Ibogaine has shown promise in anecdotal reports and preliminary studies for its ability to alleviate symptoms of neurological conditions, including addiction, and potentially Parkinson's. Its purported anti-aging and restorative properties have also garnered significant interest. While the exact mechanisms remain under investigation, one hypothesis centers on ibogaine's potential to influence gene expression, possibly through interactions with these very enhancers identified in the EMBO Reports study. The study's focus on LUHMES cells, a model for human dopaminergic neurons (the cells primarily affected in Parkinson's disease), is particularly relevant. By linking specific enhancers to genes involved in neuronal differentiation and disorders, the research provides a potential roadmap for understanding how ibogaine might influence these crucial cellular processes. Dardashti is particularly intrigued by the potential connection between the identified genetic enhancers and the "genetic rejuvenating factors" hypothesized to be influenced by ibogaine. "If ibogaine can modulate the activity of these enhancers, which are clearly linked to neurological health and disease, it could explain its reported ability to promote neuroplasticity, reduce neuroinflammation, and potentially even reverse some of the cellular damage associated with conditions like Parkinson's," he notes. The research highlights the "vast regulatory potential embedded in non-coding regions" of the genome. This aligns with the emerging understanding of ibogaine's potential to induce broad-spectrum changes in gene expression, leading to long-lasting therapeutic effects. Ibogaine by David Dardashti is committed to rigorously examining the findings of this and other related studies. This deeper dive will help determine, specifically the implications for ibogaine treatment protocols and future research directions. The goal is to move beyond anecdotal evidence and establish a solid scientific foundation for ibogaine's use in treating neurological disorders, including the potential for mitigating the progression of Parkinson's disease. About Ibogaine by David Dardashti: Ibogaine by David Dardashti is dedicated to exploring the therapeutic potential of ibogaine and promoting responsible research into its applications for addiction, neurological disorders, and overall well-being.
Associated Press
21-02-2025
- Health
- Associated Press
Ibogaine by David Dardashti Explores Groundbreaking Research Linking Genetic Enhancers to Neurological Disease Treatment, Including Parkinson's
Ibogaine by David Dardashti, a leading voice in the exploration of ibogaine's therapeutic potential, is closely analyzing a new study published in EMBO Reports that sheds light on the intricate genetic mechanisms underlying neurological disorders, including Parkinson's disease. This research, spearheaded by Associate Professor Masahito Yoshihara and colleagues, provides compelling evidence that could significantly impact the understanding and application of ibogaine treatment. The study utilized advanced genomic techniques, including CAGE, NET-CAGE, and Capture Hi-C/HiCap, to identify and characterize thousands of enhancers – non-coding DNA regions that play a crucial role in gene regulation – active during neuronal differentiation. Crucially, the researchers discovered a significant enrichment of genetic variants (SNPs) associated with Parkinson's disease and schizophrenia within these enhancers. This finding suggests that these enhancers, and the genes they regulate, are directly implicated in the development and progression of these conditions. David Dardashti, a prominent advocate for ibogaine research, recognizes the profound implications of this study for the field of ibogaine therapy. 'This research provides a critical piece of the puzzle in understanding how ibogaine may exert its remarkable effects,' Dardashti explains. 'By demonstrating the direct involvement of specific genetic enhancers in neurological disorders, it opens up exciting new avenues for exploring ibogaine's mechanism of action at a molecular level.' Ibogaine has shown promise in anecdotal reports and preliminary studies for its ability to alleviate symptoms of neurological conditions, including addiction, and potentially Parkinson's. Its purported anti-aging and restorative properties have also garnered significant interest. While the exact mechanisms remain under investigation, one hypothesis centers on ibogaine's potential to influence gene expression, possibly through interactions with these very enhancers identified in the EMBO Reports study. The study's focus on LUHMES cells, a model for human dopaminergic neurons (the cells primarily affected in Parkinson's disease), is particularly relevant. By linking specific enhancers to genes involved in neuronal differentiation and disorders, the research provides a potential roadmap for understanding how ibogaine might influence these crucial cellular processes. Dardashti is particularly intrigued by the potential connection between the identified genetic enhancers and the 'genetic rejuvenating factors' hypothesized to be influenced by ibogaine. 'If ibogaine can modulate the activity of these enhancers, which are clearly linked to neurological health and disease, it could explain its reported ability to promote neuroplasticity, reduce neuroinflammation, and potentially even reverse some of the cellular damage associated with conditions like Parkinson's,' he notes. The research highlights the 'vast regulatory potential embedded in non-coding regions' of the genome. This aligns with the emerging understanding of ibogaine's potential to induce broad-spectrum changes in gene expression, leading to long-lasting therapeutic effects. Ibogaine by David Dardashti is committed to rigorously examining the findings of this and other related studies. This deeper dive will help determine, specifically the implications for ibogaine treatment protocols and future research directions. The goal is to move beyond anecdotal evidence and establish a solid scientific foundation for ibogaine's use in treating neurological disorders, including the potential for mitigating the progression of Parkinson's disease. About Ibogaine by David Dardashti: Ibogaine by David Dardashti is dedicated to exploring the therapeutic potential of ibogaine and promoting responsible research into its applications for addiction, neurological disorders, and overall well-being. Media Contact
