Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression

Abstract Olfactory dysfunction is among the earliest features of Alzheimer’s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis showed a stage-dependent synaptic proteostasis imp...

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Autores principales:	Mercedes Lachén-Montes, Andrea González-Morales, María Victoria Zelaya, Estela Pérez-Valderrama, Karina Ausín, Isidro Ferrer, Joaquín Fernández-Irigoyen, Enrique Santamaría
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29858517ff7646809eb90c4f31b52069
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spelling	oai:doaj.org-article:29858517ff7646809eb90c4f31b520692021-12-02T16:08:00ZOlfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression10.1038/s41598-017-09481-x2045-2322https://doaj.org/article/29858517ff7646809eb90c4f31b520692017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09481-xhttps://doaj.org/toc/2045-2322Abstract Olfactory dysfunction is among the earliest features of Alzheimer’s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis showed a stage-dependent synaptic proteostasis impairment during AD evolution. In addition to progressive modulation of tau and amyloid precursor protein (APP) interactomes, network-driven proteomics revealed an early disruption of upstream and downstream p38 MAPK pathway and a subsequent impairment of Phosphoinositide-dependent protein kinase 1 (PDK1)/Protein kinase C (PKC) signaling axis in the OB from AD subjects. Moreover, a mitochondrial imbalance was evidenced by a depletion of Prohibitin-2 (Phb2) levels and a specific decrease in the phosphorylated isoforms of Phb1 in intermediate and advanced AD stages. Interestingly, olfactory Phb subunits were also deregulated across different types of dementia. Phb2 showed a specific up-regulation in mixed dementia, while Phb1 isoforms were down-regulated in frontotemporal lobar degeneration (FTLD). However, no differences were observed in the olfactory expression of Phb subunits in progressive supranuclear palsy (PSP). To sum up, our data reflect, in part, the missing links in the biochemical understanding of olfactory dysfunction in AD, unveiling Phb complex as a differential driver of neurodegeneration at olfactory level.Mercedes Lachén-MontesAndrea González-MoralesMaría Victoria ZelayaEstela Pérez-ValderramaKarina AusínIsidro FerrerJoaquín Fernández-IrigoyenEnrique SantamaríaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mercedes Lachén-Montes Andrea González-Morales María Victoria Zelaya Estela Pérez-Valderrama Karina Ausín Isidro Ferrer Joaquín Fernández-Irigoyen Enrique Santamaría Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
description	Abstract Olfactory dysfunction is among the earliest features of Alzheimer’s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis showed a stage-dependent synaptic proteostasis impairment during AD evolution. In addition to progressive modulation of tau and amyloid precursor protein (APP) interactomes, network-driven proteomics revealed an early disruption of upstream and downstream p38 MAPK pathway and a subsequent impairment of Phosphoinositide-dependent protein kinase 1 (PDK1)/Protein kinase C (PKC) signaling axis in the OB from AD subjects. Moreover, a mitochondrial imbalance was evidenced by a depletion of Prohibitin-2 (Phb2) levels and a specific decrease in the phosphorylated isoforms of Phb1 in intermediate and advanced AD stages. Interestingly, olfactory Phb subunits were also deregulated across different types of dementia. Phb2 showed a specific up-regulation in mixed dementia, while Phb1 isoforms were down-regulated in frontotemporal lobar degeneration (FTLD). However, no differences were observed in the olfactory expression of Phb subunits in progressive supranuclear palsy (PSP). To sum up, our data reflect, in part, the missing links in the biochemical understanding of olfactory dysfunction in AD, unveiling Phb complex as a differential driver of neurodegeneration at olfactory level.
format	article
author	Mercedes Lachén-Montes Andrea González-Morales María Victoria Zelaya Estela Pérez-Valderrama Karina Ausín Isidro Ferrer Joaquín Fernández-Irigoyen Enrique Santamaría
author_facet	Mercedes Lachén-Montes Andrea González-Morales María Victoria Zelaya Estela Pérez-Valderrama Karina Ausín Isidro Ferrer Joaquín Fernández-Irigoyen Enrique Santamaría
author_sort	Mercedes Lachén-Montes
title	Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
title_short	Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
title_full	Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
title_fullStr	Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
title_full_unstemmed	Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression
title_sort	olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during alzheimer’s disease progression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/29858517ff7646809eb90c4f31b52069
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Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer’s disease progression

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