Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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I'm proud to have worked on the preclinical validation of this compound in Alzheimer’s disease models and very excited to see that it has now entered a Phase I clinical trial!
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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We (Ronald van Kesteren, Rob Henning, Guus Smit, Wiep Scheper, Maarten Witte) recently published a paper in ACTA Neuropathologica Communications on the reversible hyperphosphorylated tau accumulation we observed after inducing torpor in human tau expressing mice.As tau protein hyperphosphorylation and aggregation are key pathological events in neurodegenerative tauopathies such as Alzheimer's disease, we believe that torpor in mice offers a quick and standardized method to study tau phosphorylation, accumulation and clearance in mouse models relevant for neurodegeneration, as well as opportunities to discover new targets for the treatment of human tauopathies.
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Christine De Veij Mestdagh, PhD
See AlsoChristine De Veij Mestdagh, PhD on LinkedIn: Torpor induces reversible tau hyperphosphorylation and accumulation in…Centrum Menopause Support Review: Does It Work?fotowandenshop.nl Reviews | scam, legit or safe check | ScamadviserChristine De Veij Mestdagh, PhD on LinkedIn: Sulfateq GEN Press releasePostdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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Last month we (me, Ronald van Kesteren, Rob Henning and Guus Smit) published a review on hibernation-derived mitochondrial targeting against Alzheimer's disease and the lessons we can learn from hibernation. It is a nice follow-up on the experimental chapters of my thesis which focussed on exploring molecular mechanisms of mouse hibernation for novel therapeutic angles in Alzheimer’s disease. Abstract: Alzheimer's disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the mitochondrial cascade hypothesis is gaining attention. Accumulating evidence shows that mitochondrial dysfunction is a driving force behind synaptic dysfunction and cognitive decline in AD patients. However, therapies targeting the mitochondria in AD have proven unsuccessful so far, and out-of-the-box options, such as hibernation-derived mitochondrial mechanisms, may provide valuable new insights. Hibernators uniquely and rapidly alternate between suppression and re-activation of the mitochondria while maintaining a sufficient energy supply and without acquiring ROS damage. Here, we briefly give an overview of mitochondrial dysfunction in AD, how it affects synaptic function, and why mitochondrial targeting in AD has remained unsuccessful so far. We then discuss mitochondria in hibernation and daily torpor in mice, covering current advancements in hibernation-derived mitochondrial targeting strategies. We conclude with new ideas on how hibernation-derived dual mitochondrial targeting of both the ATP and ROS pathways may boost mitochondrial health and induce local synaptic protein translation to increase synaptic function and plasticity. Further exploration of these mechanisms may provide more effective treatment options for AD in the future.
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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https://lnkd.in/ey2fKHCdhttps://rdcu.be/c1hhxVery proud that our work, on the hibernation-derived compound, SUL-138, and its promising effects in an Alzheimer’s disease mouse model, is now out in Alzheimer's Research and Therapy! This is the 1st publication of the HiberTreat consortium (TKI - @Health Holland funded), which is a collaborative effort of the dept. of molecular and cellular neurobiology, , VU - Prof. dr. Ronald van Kesteren & the dept. of clinical pharmacy and pharmacology - Prof. dr. Rob Henning, UMCG & the Amsterdam UMC - Alzheimercentrum Amsterdam - prof. dr. Philip Scheltens & Sulfateq B.V. to find common beneficial mechanisms of hibernation and hibernation-derived compounds (SUL compounds) that counter Alzheimer's disease progression. In this study we show that SUL-138 treatment rescues long-term potentiation and hippocampal memory impairments and decreases beta-amyloid plaque load in APP/PS1 mice. This was paralleled by a partial rescue of dysregulated protein expression in APP/PS1 mice as assessed by mass spectrometry-based proteomics. In-depth analysis of protein expression revealed a prominent effect of SUL-138 in APP/PS1 mice on mitochondrial protein expression. SUL-138 increased the levels of proteins involved in fatty acid metabolism in both wildtype and APP/PS1 mice. Additionally, in APP/PS1 mice only, SUL-138 increased the levels of proteins involved in glycolysis and amino acid metabolism pathways, indicating that SUL-138 rescues mitochondrial impairments that are typically observed in AD.Our study demonstrates a SUL-138-induced shift in metabolic input towards the electron transport chain in synaptic mitochondria, coinciding with increased synaptic plasticity and memory. Targeting mitochondrial bioenergetics might provide a promising new way to treat cognitive impairments in AD and reduce disease progression.
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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Presented a Plenary oral at the International Hibernation Symposium (https://lnkd.in/dmbpvptC) last week. It was great to be part of this well-organized hybrid conference and to be able to see the work of a wide range of multi-disciplinary top hibernation researchers. Interesting presentations and discussions, looking forward to the next meeting in 2024! Thank you Rob Henning, Hjalmar Bouma and Roelof A. Hut (Rijksuniversiteit Groningen) for organizing!#research #conference
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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Part of my PhD work, focussing on enhanced synaptic plasticity in daily torpor (hibernating) mice and its use in Alzheimer's Disease, has now been published! by SpringerNature Digital in Nature Scientific Reports, see link: https://rdcu.be/cqKIF#neuroscience #research #brain #alzheimer #hibernation #phd
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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Proud to be part of this advancement in research into mitochondrial priming against Alzheimer's disease. Very exciting new collaboration! Looking forward to future results and expansion of knowledge on this promising compound.
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Christine De Veij Mestdagh, PhD
Postdoctoral researcher Alzheimercentrum | Contracted preclinical research | Neuroscience
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