Olfactory proteotyping: towards the enlightenment of the neurodegeneration
Joaquín Fernández-Irigoyen
Enrique Santamaría
摘要：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) (Doty, 2012;Attems et al., 2014), which may vary from severe smell loss (e.g., Alzheimer's and Parkinson's diseases) to relatively moderate loss (e.g., progressive supranuclear palsy) (Doty, 2017). Recently, a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb (OB) during the neurodegenerative process (Attems et al., 2014;Rey et al., 2018). For instance, the double-transgenic APP/PS1 mouse model of Alzheimer's disease (AD) develops early proteomic disturbances accompanied by a specifc modulation of the focal adhesion kinase (FAK) and mitogen-activated 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 (Lachen-Montes et al., 2016). Nevertheless, there are currently specific questions which should be addressed in human neurodegeneration: Does the loss of smell precede the onset of ND-specifc 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 di?erent neurological backgrounds?
机标关键词：
资助基金：funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO)(SAF2014-59340-R)Department of Economic Development from Government of Navarra(PC023-PC024)Department of Economic Development from Government of Navarra( PC025)Department of Economic Development from Government of Navarra( PC081-82 and PI059)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：3( 979-981 )