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The olfactory bulb proteotype differs across frontotemporal dementia spectrum.
Journal article

The olfactory bulb proteotype differs across frontotemporal dementia spectrum.

  • Lachén-Montes M Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain.
  • González-Morales A Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain.
  • Schvartz D Translational Biomarker Group, Department of Human Protein Sciences, University of Geneva, Rue Michel Servet 1, 1211 Geneve 4, Switzerland.
  • Zelaya MV Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain; Pathological Anatomy Department, Complejo Hospitalario de Navarra (CHN), Pamplona, Spain.
  • Ausin K Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain.
  • Fernández-Irigoyen J Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain.
  • Sánchez JC Translational Biomarker Group, Department of Human Protein Sciences, University of Geneva, Rue Michel Servet 1, 1211 Geneve 4, Switzerland.
  • Santamaría E Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain. Electronic address: esantamma@navarra.es.
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  • 2019-04-19
Published in:
  • Journal of proteomics. - 2019
Aged
Aged, 80 and over
Female
Frontotemporal Dementia
Humans
Male
Middle Aged
Olfactory Bulb
Proteome
Proteomics
Supranuclear Palsy, Progressive
English Mild olfactory dysfunction has been observed in frontotemporal dementias (FTD). However, the underlying molecular mechanisms associated to this deficit are poorly understood. We applied quantitative proteomics to analyze pathological effects on the olfactory bulb (OB) from progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTLD-TDP43) subjects respect to elderly non-FTD group. Our data revealed: i) a mitochondrial and calcium homeostasis impairment in PSP and ii) a disruption of protein synthesis and vesicle trafficking in FTLD-TDP43. Although differential OB proteomes clearly differ between both FTD phenotypes, functional analyses pointed out an imbalance in survival signaling in both pathologies. A common alteration of olfactory mitogen-activated protein kinases (MAPKs), calcium/calmodulin dependent protein kinase II (CAMKII), and protein kinase C (PKC) signaling pathways was observed in PSP and FTLD subjects. In contrast, a specific shut off in mitogen-activated protein kinase kinase 4 (SEK1/MKK4)/stress-activated protein kinase (SAPK) axis was exclusively observed in PSP, whereas a specific phosphoinositide-dependent protein kinase 1 (PDK1) inactivation was observed in FTLD-TDP43. In summary, our data contribute to a better understanding of the molecular mechanisms that are modulated in PSP and FTLD-TDP43 at olfactory level, highlighting cross-disease similarities and differences in the regulation of survival pathways across FTD spectrum. SIGNIFICANCE: This work reflects differential olfactory molecular disarrangements in PSP and FTLD-TDP43, two clinically similar FTD disorders, but with different neuropathological signature. Besides FTDs present mild olfactory dysfunction, our data provide basic information for understanding the implication of the OB in the pathophysiology of FTDs.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/43869
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