A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease

Artículo escrito por un elevado número de autores, solo se referencia el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAM

Detalles Bibliográficos
Autores: Hampel, Harald, Avila, Jesus
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/711230
Acceso en línea:http://hdl.handle.net/10486/711230
https://dx.doi.org/10.3389/fimmu.2020.00456
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
Anti-inflammatory therapy
Biomarkers
Microglia
Neuroinflammation
Neuroinflammatory pathways
Precision medicine
Systems biology
Biología y Biomedicina / Biología
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spelling A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's diseaseHampel, HaraldAvila, JesusAlzheimer's diseaseAnti-inflammatory therapyBiomarkersMicrogliaNeuroinflammationNeuroinflammatory pathwaysPrecision medicineSystems biologyBiología y Biomedicina / BiologíaArtículo escrito por un elevado número de autores, solo se referencia el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMNeuroinflammation commences decades before Alzheimer's disease (AD) clinical onset and represents one of the earliest pathomechanistic alterations throughout the AD continuum. Large-scale genome-wide association studies point out several genetic variants—TREM2, CD33, PILRA, CR1, MS4A, CLU, ABCA7, EPHA1, and HLA-DRB5-HLA-DRB1—potentially linked to neuroinflammation. Most of these genes are involved in proinflammatory intracellular signaling, cytokines/interleukins/cell turnover, synaptic activity, lipid metabolism, and vesicle trafficking. Proteomic studies indicate that a plethora of interconnected aberrant molecular pathways, set off and perpetuated by TNF-α, TGF-β, IL-1β, and the receptor protein TREM2, are involved in neuroinflammation. Microglia and astrocytes are key cellular drivers and regulators of neuroinflammation. Under physiological conditions, they are important for neurotransmission and synaptic homeostasis. In AD, there is a turning point throughout its pathophysiological evolution where glial cells sustain an overexpressed inflammatory response that synergizes with amyloid-β and tau accumulation, and drives synaptotoxicity and neurodegeneration in a self-reinforcing manner. Despite a strong therapeutic rationale, previous clinical trials investigating compounds with anti-inflammatory properties, including non-steroidal anti-inflammatory drugs (NSAIDs), did not achieve primary efficacy endpoints. It is conceivable that study design issues, including the lack of diagnostic accuracy and biomarkers for target population identification and proof of mechanism, may partially explain the negative outcomes. However, a recent meta-analysis indicates a potential biological effect of NSAIDs. In this regard, candidate fluid biomarkers of neuroinflammation are under analytical/clinical validation, i.e., TREM2, IL-1β, MCP-1, IL-6, TNF-α receptor complexes, TGF-β, and YKL-40. PET radio-ligands are investigated to accomplish in vivo and longitudinal regional exploration of neuroinflammation. Biomarkers tracking different molecular pathways (body fluid matrixes) along with brain neuroinflammatory endophenotypes (neuroimaging markers), can untangle temporal–spatial dynamics between neuroinflammation and other AD pathophysiological mechanisms. Robust biomarker–drug codevelopment pipelines are expected to enrich large-scale clinical trials testing new-generation compounds active, directly or indirectly, on neuroinflammatory targets and displaying putative disease-modifying effects: novel NSAIDs, AL002 (anti-TREM2 antibody), anti-Aβ protofibrils (BAN2401), and AL003 (anti-CD33 antibody). As a next step, taking advantage of breakthrough and multimodal techniques coupled with a systems biology approach is the path to pursue for developing individualized therapeutic strategies targeting neuroinflammation under the framework of precision medicineFrontiers Media S.A.Facultad de Ciencias20202020-03-31research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711230https://dx.doi.org/10.3389/fimmu.2020.00456reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7112302026-06-23T12:46:27Z
dc.title.none.fl_str_mv A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
title A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
spellingShingle A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
Hampel, Harald
Alzheimer's disease
Anti-inflammatory therapy
Biomarkers
Microglia
Neuroinflammation
Neuroinflammatory pathways
Precision medicine
Systems biology
Biología y Biomedicina / Biología
title_short A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
title_full A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
title_fullStr A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
title_full_unstemmed A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
title_sort A path toward precision medicine for neuroinflammatory mechanisms in alzheimer's disease
dc.creator.none.fl_str_mv Hampel, Harald
Avila, Jesus
author Hampel, Harald
author_facet Hampel, Harald
Avila, Jesus
author_role author
author2 Avila, Jesus
author2_role author
dc.contributor.none.fl_str_mv Facultad de Ciencias
dc.subject.none.fl_str_mv Alzheimer's disease
Anti-inflammatory therapy
Biomarkers
Microglia
Neuroinflammation
Neuroinflammatory pathways
Precision medicine
Systems biology
Biología y Biomedicina / Biología
topic Alzheimer's disease
Anti-inflammatory therapy
Biomarkers
Microglia
Neuroinflammation
Neuroinflammatory pathways
Precision medicine
Systems biology
Biología y Biomedicina / Biología
description Artículo escrito por un elevado número de autores, solo se referencia el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAM
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-03-31
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/711230
https://dx.doi.org/10.3389/fimmu.2020.00456
url http://hdl.handle.net/10486/711230
https://dx.doi.org/10.3389/fimmu.2020.00456
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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