Thomas Sandmann
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View article: Towards an AI biomedical scientist: Accelerating discoveries in neurodegenerative disease
Towards an AI biomedical scientist: Accelerating discoveries in neurodegenerative disease Open
Despite major advances in Alzheimer's disease and related diseases (ADRD) research, the translation of discoveries into impactful clinical interventions remains slow. Overwhelming data complexity, fragmented knowledge, and prolonged resear…
View article: CNS-PENETRANT NLRP3 INHIBITOR ACHIEVES DURABLE WEIGHT LOSS AND REVERSES HYPOTHALAMIC INFLAMMATION IN DIET-INDUCED OBESITY
CNS-PENETRANT NLRP3 INHIBITOR ACHIEVES DURABLE WEIGHT LOSS AND REVERSES HYPOTHALAMIC INFLAMMATION IN DIET-INDUCED OBESITY Open
The NLRP3 inflammasome is a key mediator of innate immunity that integrates inflammatory and metabolic stress signals. Increased and/or chronic activation of this critical pathway has been implicated in obesity, with hypothalamic neuroinfl…
View article: Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial
Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial Open
Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator …
View article: Anti-Aβ immunotherapy-mediated amyloid clearance attenuates microglial activation without inducing exhaustion at residual plaques
Anti-Aβ immunotherapy-mediated amyloid clearance attenuates microglial activation without inducing exhaustion at residual plaques Open
Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer’s disease. Efficient amyloid plaque clearance has been proven in clinical trials testing …
View article: Lysosomes cell autonomously regulate myeloid cell states and immune responses
Lysosomes cell autonomously regulate myeloid cell states and immune responses Open
Myeloid cells maintain tissue homeostasis via the recognition, engulfment, and lysosomal clearance of dying cells and cellular debris, which is often accompanied by changes from homeostatic to reactive states. While a role for phagocytic r…
View article: DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response
DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Reviewer #2 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Reviewer #2 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Reviewer #1 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Reviewer #1 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Author response: DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Author response: DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Reviewer #3 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Reviewer #3 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration
Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration Open
Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43) pathology (FTLD- GRN ). Multiple therapeutic strategies are in clinical development to restore PGRN…
View article: The Genetic Drivers of Juvenile, Young, and Early‐Onset Parkinson's Disease in India
The Genetic Drivers of Juvenile, Young, and Early‐Onset Parkinson's Disease in India Open
Background Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome‐wide association study (GWAS) identifi…
View article: DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response
DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Reviewer #2 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Reviewer #2 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Reviewer #3 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
Reviewer #3 (Public Review): DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response
DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response Open
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolo…
View article: Rescue of FTLD-associated TDP-43 pathology and neurodegeneration by peripheral AAV-mediated expression of brain-penetrant progranulin
Rescue of FTLD-associated TDP-43 pathology and neurodegeneration by peripheral AAV-mediated expression of brain-penetrant progranulin Open
Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology (FTLD- GRN ). Multiple therapeutic strategies are in clinical development to restore PGRN levels in the CNS, including…
View article: The genetic drivers of juvenile, young, and early-onset Parkinson’s Disease in India
The genetic drivers of juvenile, young, and early-onset Parkinson’s Disease in India Open
Background Recent studies have advanced our understanding of the genetic drivers of Parkinson’s Disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD GWAS study identified 90 independent risk loc…
View article: Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier
Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier Open
Antisense oligonucleotides (ASO) are promising therapies for neurological disorders, though they are unable to cross the blood-brain barrier (BBB) and must be delivered directly to the central nervous system (CNS). Here, we use a human tra…
View article: Additional file 11 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 11 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 11: Table s3. Plaque Count Whole-Bean
View article: Additional file 15 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 15 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 15: Table s7. methoxyx04_baseline_abundance.
View article: Additional file 13 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 13 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 13: Table s5. microglia baseline abundance.
View article: Additional file 16 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 16 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 16: Table s8. methoxyx04_diff_abundance analysis
View article: Additional file 12 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 12 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 12: Table s4. Gene Sets in Figure 3 and Figure 4.
View article: Additional file 14 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
Additional file 14 of Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia Open
Additional file 14: Table s6. microglia diff abundance analysis.