Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells
Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prio...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/33695 |
| Acceso en línea: | https://doi.org/10.1111/bpa.13235 https://hdl.handle.net/10578/33695 |
| Access Level: | acceso abierto |
| Palabra clave: | Amyloid-β ANXA2 Astroglia GFAP IBA1 Microglia Neurodegeneration PYK2 Synapse Tau |
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Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cellsAstillero López, VerónicaVillar Conde, SandraGonzález Rodríguez, MelaniaFlores Cuadrado, Alicia MaríaÚbeda Bañón, Isabel MaríaSaiz Sánchez, DanielMartínez Marcos, Alino JoséAmyloid-βANXA2AstrogliaGFAPIBA1MicrogliaNeurodegenerationPYK2SynapseTauAlzheimer’s disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron–glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and nonAD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aß and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aß and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aß plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aß pathology through microglial and astroglial cells in the human EC in AD.Wiley202420242024info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://doi.org/10.1111/bpa.13235https://hdl.handle.net/10578/33695reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésPID2019-108659RB-I00SBPLY/17/180501/000430SBPLY/21/180501/000092022-GRIN-34200info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/336952026-05-27T07:36:41Z |
| dc.title.none.fl_str_mv |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| title |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| spellingShingle |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells Astillero López, Verónica Amyloid-β ANXA2 Astroglia GFAP IBA1 Microglia Neurodegeneration PYK2 Synapse Tau |
| title_short |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| title_full |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| title_fullStr |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| title_full_unstemmed |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| title_sort |
Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells |
| dc.creator.none.fl_str_mv |
Astillero López, Verónica Villar Conde, Sandra González Rodríguez, Melania Flores Cuadrado, Alicia María Úbeda Bañón, Isabel María Saiz Sánchez, Daniel Martínez Marcos, Alino José |
| author |
Astillero López, Verónica |
| author_facet |
Astillero López, Verónica Villar Conde, Sandra González Rodríguez, Melania Flores Cuadrado, Alicia María Úbeda Bañón, Isabel María Saiz Sánchez, Daniel Martínez Marcos, Alino José |
| author_role |
author |
| author2 |
Villar Conde, Sandra González Rodríguez, Melania Flores Cuadrado, Alicia María Úbeda Bañón, Isabel María Saiz Sánchez, Daniel Martínez Marcos, Alino José |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
Amyloid-β ANXA2 Astroglia GFAP IBA1 Microglia Neurodegeneration PYK2 Synapse Tau |
| topic |
Amyloid-β ANXA2 Astroglia GFAP IBA1 Microglia Neurodegeneration PYK2 Synapse Tau |
| description |
Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron–glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and nonAD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aß and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aß and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aß plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aß pathology through microglial and astroglial cells in the human EC in AD. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://doi.org/10.1111/bpa.13235 https://hdl.handle.net/10578/33695 |
| url |
https://doi.org/10.1111/bpa.13235 https://hdl.handle.net/10578/33695 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
PID2019-108659RB-I00 SBPLY/17/180501/000430 SBPLY/21/180501/00009 2022-GRIN-34200 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
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Wiley |
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reponame:RUIdeRA. Repositorio Institucional de la UCLM instname:Universidad de Castilla-La Mancha |
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Universidad de Castilla-La Mancha |
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RUIdeRA. Repositorio Institucional de la UCLM |
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RUIdeRA. Repositorio Institucional de la UCLM |
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