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| Home > Publications Database > Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery. |
| Home > Publications Database > Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery. |
| Journal Article (Review Article) | DZNE-2021-01080 |
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2021
Elsevier Science
Amsterdam [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.neuropharm.2020.108081
Abstract: When Alzheimer's disease (AD) disease-modifying therapies will be available, global healthcare systems will be challenged by a large-scale demand for clinical and biological screening. Validation and qualification of globally accessible, minimally-invasive, and time-, cost-saving blood-based biomarkers need to be advanced. Novel pathophysiological mechanisms (and related candidate biomarkers) - including neuroinflammation pathways (TREM2 and YKL-40), axonal degeneration (neurofilament light chain protein), synaptic dysfunction (neurogranin, synaptotagmin, α-synuclein, and SNAP-25) - may be integrated into an expanding pathophysiological and biomarker matrix and, ultimately, integrated into a comprehensive blood-based liquid biopsy, aligned with the evolving ATN + classification system and the precision medicine paradigm. Liquid biopsy-based diagnostic and therapeutic algorithms are increasingly employed in Oncology disease-modifying therapies and medical practice, showing an enormous potential for AD and other brain diseases as well. For AD and other neurodegenerative diseases, newly identified aberrant molecular pathways have been identified as suitable therapeutic targets and are currently investigated by academia/industry-led R&D programs, including the nerve-growth factor pathway in basal forebrain cholinergic neurons, the sigma1 receptor, and the GTPases of the Rho family. Evidence for a clinical long-term effect on cognitive function and brain health span of cholinergic compounds, drug candidates for repositioning programs, and non-pharmacological multidomain interventions (nutrition, cognitive training, and physical activity) is developing as well. Ultimately, novel pharmacological paradigms, such as quantitative systems pharmacology-based integrative/explorative approaches, are gaining momentum to optimize drug discovery and accomplish effective pathway-based strategies for precision medicine. This article is part of the special issue on 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
Keyword(s): Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: drug therapy (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Animals (MeSH) ; Anti-Inflammatory Agents: administration & dosage (MeSH) ; Anti-Inflammatory Agents: metabolism (MeSH) ; Drug Discovery: methods (MeSH) ; Drug Discovery: trends (MeSH) ; Drug Repositioning: methods (MeSH) ; Drug Repositioning: trends (MeSH) ; Forecasting (MeSH) ; Humans (MeSH) ; Intracellular Fluid: drug effects (MeSH) ; Intracellular Fluid: metabolism (MeSH) ; Liquid Biopsy: methods (MeSH) ; Liquid Biopsy: trends (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Pharmacology, Clinical: methods (MeSH) ; Pharmacology, Clinical: trends (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Signal Transduction: drug effects (MeSH) ; Signal Transduction: physiology (MeSH) ; Systems Biology: methods (MeSH) ; Systems Biology: trends (MeSH) ; Alzheimer's disease ; Blood biomarkers ; Disease-modifying therapies ; Liquid biopsy ; Precision medicine ; Systems pharmacology
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