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000155926 0247_ $$2doi$$a10.1016/j.neuropharm.2020.108081
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000155926 037__ $$aDZNE-2021-01080
000155926 041__ $$aEnglish
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000155926 1001_ $$aVergallo, Andrea$$b0
000155926 245__ $$aFuture avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.
000155926 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2021
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000155926 520__ $$aWhen 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'.
000155926 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0
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000155926 650_7 $$2Other$$aAlzheimer's disease
000155926 650_7 $$2Other$$aBlood biomarkers
000155926 650_7 $$2Other$$aDisease-modifying therapies
000155926 650_7 $$2Other$$aLiquid biopsy
000155926 650_7 $$2Other$$aPrecision medicine
000155926 650_7 $$2Other$$aSystems pharmacology
000155926 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000155926 650_2 $$2MeSH$$aAlzheimer Disease: drug therapy
000155926 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000155926 650_2 $$2MeSH$$aAnimals
000155926 650_2 $$2MeSH$$aAnti-Inflammatory Agents: administration & dosage
000155926 650_2 $$2MeSH$$aAnti-Inflammatory Agents: metabolism
000155926 650_2 $$2MeSH$$aDrug Discovery: methods
000155926 650_2 $$2MeSH$$aDrug Discovery: trends
000155926 650_2 $$2MeSH$$aDrug Repositioning: methods
000155926 650_2 $$2MeSH$$aDrug Repositioning: trends
000155926 650_2 $$2MeSH$$aForecasting
000155926 650_2 $$2MeSH$$aHumans
000155926 650_2 $$2MeSH$$aIntracellular Fluid: drug effects
000155926 650_2 $$2MeSH$$aIntracellular Fluid: metabolism
000155926 650_2 $$2MeSH$$aLiquid Biopsy: methods
000155926 650_2 $$2MeSH$$aLiquid Biopsy: trends
000155926 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000155926 650_2 $$2MeSH$$aPharmacology, Clinical: methods
000155926 650_2 $$2MeSH$$aPharmacology, Clinical: trends
000155926 650_2 $$2MeSH$$aReceptors, Immunologic: metabolism
000155926 650_2 $$2MeSH$$aSignal Transduction: drug effects
000155926 650_2 $$2MeSH$$aSignal Transduction: physiology
000155926 650_2 $$2MeSH$$aSystems Biology: methods
000155926 650_2 $$2MeSH$$aSystems Biology: trends
000155926 7001_ $$aCaraci, Filippo$$b1
000155926 7001_ $$aCuello, A Claudio$$b2
000155926 7001_ $$aLemercier, Pablo$$b3
000155926 7001_ $$aVellas, Bruno$$b4
000155926 7001_ $$aGiudici, Kelly Virecoulon$$b5
000155926 7001_ $$aHampel, Harald$$b6
000155926 7001_ $$aBaldacci, Filippo$$b7
000155926 7001_ $$0P:(DE-2719)2810511$$aHänisch, Britta$$b8
000155926 7001_ $$aHaberkamp, Marion$$b9
000155926 7001_ $$aBroich, Karl$$b10
000155926 7001_ $$aNisticò, Robert$$b11
000155926 7001_ $$aEmanuele, Enzo$$b12
000155926 7001_ $$aLlavero, Francisco$$b13
000155926 7001_ $$aZugaza, José L$$b14
000155926 7001_ $$aLucía, Alejandro$$b15
000155926 7001_ $$aGiacobini, Ezio$$b16
000155926 7001_ $$0P:(DE-2719)2810761$$aLista, Simone$$b17
000155926 7001_ $$aInitiative, Alzheimer Precision Medicine$$b18$$eCollaboration Author
000155926 773__ $$0PERI:(DE-600)1500655-4$$a10.1016/j.neuropharm.2020.108081$$gVol. 185, p. 108081 -$$p108081$$tNeuropharmacology$$v185$$x0028-3908$$y2021
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