Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer's disease  

作　　者：Wei Xiong Ye Liu Heng Zhou Junyi Li Shuili Jing Cailei Jiang Mei Li Yan He Qingsong Ye 

机构地区：[1]Center of Regenerative Medicine,Department of Stomatology,Renmin Hospital of Wuhan University,Wuhan,Hubei,China [2]Institute of Regenerative and Translational Medicine,Tianyou Hospital,Wuhan University of Science and Technology,Wuhan,China [3]Department of Oral Science,Faculty of Dentistry,University of Otago,Dunedin,New Zealand [4]Department of Oral and Maxillofacial Surgery,Massachusetts General Hospital,Harvard Medical School,Boston,MA,USA [5]Department of Stomatology,Linhai Second People’s Hospital,Linhai,Zhejiang,China

出　　处：《International Journal of Oral Science》2024年第4期657-670,共14页国际口腔科学杂志(英文版)

基　　金：supported by the key R&D Program of Hubei Province of China(YFXM2022000264);key Project of Ministry of Science and Technology China(2022YFC2504200);National Natural Science Foundation of China(U22A20314);Chutian Researcher Project(X22020024).

摘　　要：Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTgAD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by h DPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of h DPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

关 键 词：protective ALZHEIMER NRF2 

分 类 号：R749.16[医药卫生—神经病学与精神病学]