Article record

细胞氧化还原状态与认知衰退中的嗅觉改变相关

Cellular redox status is linked to olfactory alterations in cognitive decline.

基础研究鼻科IF 15.9Q1

文献信息

PMID	42731289
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Riikka Lampinen 查看其他 15 位作者 Alexey M Afonin；Laura Mussalo；Simone Avesani；Tana Zavodna；Emily Feneberg；Zdenek Krejcik；Jan Topinka；Sweelin Chew；Heikki Löppönen；Tarja Malm；Rosalba Giugno；Anthony R White；Anne M Koivisto；Elina Penttilä；Katja M Kanninen
作者单位	A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio, 70210, Finland. 查看其他 7 条单位信息 Department of Computer Science, University of Verona, Strada le Grazie 15, Verona, 37134, Italy.；Department of Toxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, Prague, 142 20, Czech Republic.；Department of Neurology, Klinikum Rechts der Isar of the Technical University of Munich, Ismaninger Strasse 22, Munich, 81675, Germany.；Department of Otorhinolaryngology, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland.；Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, 4006, Australia.；NeuroCentre, Kuopio University Hospital, Kuopio, 70210, Finland; Department of Geriatrics, Helsinki University Hospital, Haartmaninkatu 8, Helsinki, 00014, Finland; Department of Neurosciences, Faculty of Medicine, University of Helsinki, Haartmaninkatu 4, Helsinki, 00014, Finland.；A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio, 70210, Finland. Electronic address: katja.kanninen@uef.fi.
期刊	Redox biology
SCI 分区	Q1
IF	15.9
研究类型	基础研究 · 基础／转化
所属专科	鼻科

中文摘要

越来越多的证据表明，嗅觉功能障碍以及嗅觉区域的疾病相关病理改变在阿尔茨海默病（AD）早期即已出现，而AD是最常见的神经退行性疾病。氧化应激与AD相关的脑内改变密切相关，但对外周嗅觉组织中的氧化还原稳态及其与早期AD相关嗅觉功能障碍的联系知之甚少。嗅觉黏膜（OM）位于鼻腔顶部，是通过气味检测并将这些信号经嗅神经传递至大脑的主要嗅觉器官。本研究收集了认知健康供者、轻度认知障碍（MCI）个体和AD患者的OM患者来源活检组织。对活检组织进行鸟枪法蛋白质组学分析，为与早期AD和嗅觉功能障碍相关的分子机制提供了新见解，嗅觉功能障碍通过气味识别测试进行评估。此外，研究还利用microRNA测序以及对活检来源OM原代细胞中电子载体、辅因子和谷胱甘肽的定量分析，将这些发现与细胞氧化还原状态联系起来。结果显示，在MCI和AD的OM中存在线粒体改变以及细胞抗氧化防御的变化，特别是NRF2通路可能受到抑制，这些改变与气味识别受损相关。理解嗅觉系统和嗅觉中发生的早期细胞和分子变化，可能有助于早期识别有AD发病风险的个体以及AD中OM的病理生理改变。

英文摘要

Growing evidence demonstrates that olfactory dysfunction and disease-related pathology in the olfactory areas occur early in Alzheimer's disease (AD), which is the most common neurodegenerative disorder. Oxidative stress is strongly linked to AD-associated changes in the brain, yet very little is known about redox homeostasis in the peripheral olfactory tissues, and its link to olfactory dysfunction associated with early AD. The olfactory mucosa (OM), located at the rooftop of the nasal cavity is the primary organ for olfaction through odorant detection and transmission of these signals to the brain via the olfactory nerves. This study collected patient-derived biopsies of the OM from cognitively healthy donors, individuals with mild cognitive impairment (MCI) and AD. Shotgun proteomics of the biopsies provided new insights into the molecular mechanisms associated with early AD and olfactory dysfunction, which was assessed by odor identification testing. Furthermore, microRNA sequencing and quantitative analyses of electron carriers, cofactors and glutathione from the biopsy-derived primary cells of the OM were used to link these findings to cellular redox status. The results revealed mitochondrial changes and alterations to cellular defense against oxidative stress, specifically the potentially dampened NRF2 pathway, in MCI and AD OM, which were linked to impairments in odor identification. Understanding the early cellular and molecular changes occurring in the olfactory system and olfaction could aid in the early identification of individuals at risk of developing AD and pathophysiological changes of the OM in AD.