中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (6): 979-981.doi: 10.4103/1673-5374.249220

• 观点:退行性病与再生 • 上一篇    下一篇

嗅觉蛋白质分型:迈向神经变性的初始

  

  • 出版日期:2019-06-15 发布日期:2019-06-15

Olfactory proteotyping: towards the enlightenment of the neurodegeneration

Joaquín Fernández-Irigoyen, Enrique Santamaría   

  1. Proteored-Institute of Health Carlos III (ISCIII), Clinical Neuroproteomics Unit, Navarrabiomed, Navarra Health Department, Public University of Navarra, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Enrique Santamaría, PhD, esantamma@navarra.es.
  • Supported by:

    This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (No. SAF2014-59340-R), Department of Economic Development from Government of Navarra (No. PC023-PC024, PC025, PC081-82 and PI059) and Obra Social la Caixa to ES. The Proteomics Unit of Navarrabiomed is a member of Proteored, PRB3-ISCIII, and was supported by grant PT17/0019 to JFI, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF.

摘要:

orcid: 0000-0001-8046-8102 (Enrique Santamaría)

Abstract:

Although phylogenetically ancient, the olfactory system has received less attention than other sensorial systems. However, olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases (NDs), which may vary from severe smell loss (e.g., Alzheimer’s and Parkinson’s diseases) to relatively moderate loss (e.g., progressive supranuclear palsy). Recently, a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb (OB) during the neurodegenerative process. For instance, the double-transgenic APP/PS1 mouse model of Alzheimer’s disease (AD) develops early proteomic disturbances accompanied by a specific modulation of the focal adhesion kinase (FAK) and mitogen-ac-tivated protein kinase (MAPK) dynamics at the level of the OB, demonstrating that olfactory molecular alterations occur prior to β-amyloid plaque appearance and memory impairments in APP/ PS1 transgenic mice. Nevertheless, there are currently specific questions which should be addressed in human neurodegeneration: Does the loss of smell precede the onset of ND-specific neuropathological features? What is the metabolic impairment induced by protein inclusions in the OB? Is it disease-specific or tauopathy/synucleinopathy-dependent? How the neuropathological substrates modulate their constitutive interactome at olfactory level? Are there common olfactory targets across different neurological backgrounds?