PMID- 38183387
OWN - NLM
STAT- MEDLINE
DCOM- 20240321
LR  - 20240322
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 11
IP  - 11
DP  - 2024 Mar
TI  - SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 
      5'UTR-dependent ADAM10 Translation Initiation.
PG  - e2305260
LID - 10.1002/advs.202305260 [doi]
LID - 2305260
AB  - It is long been suggested that one-carbon metabolism (OCM) is associated with 
      Alzheimer's disease (AD), whereas the potential mechanisms remain poorly 
      understood. Taking advantage of chemical biology, that mitochondrial serine 
      hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM 
      metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. 
      That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' 
      untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is 
      found. SHMT2, which is identified as a target gene of KEN and the 
      5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 
      translation in vitro and in vivo. SHMT2 controls AD signaling pathways through 
      binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by 
      direct interaction with GAGGG motif, whereas this motif affected ribosomal 
      scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN 
      exhibits therapeutic potential for AD by linking OCM with RNA processing, in 
      which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif 
      and promoting the 5'UTR-dependent ADAM10 translation initiation.
CI  - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Song, Li
AU  - Song L
AUID- ORCID: 0009-0009-2148-970X
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Pan, Qiu-Ling
AU  - Pan QL
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Zhou, Gui-Feng
AU  - Zhou GF
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Liu, Sheng-Wei
AU  - Liu SW
AD  - Department of Pharmacy, Yongchuan Hospital of Chongqing Medical University, 
      Chongqing, 402160, China.
FAU - Zhu, Bing-Lin
AU  - Zhu BL
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Lin, Pei-Jia
AU  - Lin PJ
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Hu, Xiao-Tong
AU  - Hu XT
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
AD  - Department of Health Management, Daping Hospital, Army Medical university, 
      Chongqing, 400042, China.
FAU - Zha, Jing-Si
AU  - Zha JS
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
AD  - Department of Internal Medicine, The Southwest University Hospital, Chongqing, 
      400715, China.
FAU - Long, Yan
AU  - Long Y
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
AD  - Department of Geriatric Medicine, Daping Hospital, Army Medical university, 
      Chongqing, 400042, China.
FAU - Luo, Biao
AU  - Luo B
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Chen, Jian
AU  - Chen J
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Tang, Ying
AU  - Tang Y
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
AD  - Department of Neurology, West China Hospital, Sichuan University, Chengdu, 
      610041, China.
FAU - Tang, Jing
AU  - Tang J
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Xiang, Xiao-Jiao
AU  - Xiang XJ
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing, 400010, China.
FAU - Xie, Xiao-Yong
AU  - Xie XY
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Deng, Xiao-Juan
AU  - Deng XJ
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Chen, Guo-Jun
AU  - Chen GJ
AD  - Department of Neurology, Chongqing Key Laboratory of Major Neurological and 
      Mental Disorders, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing, 400016, China.
LA  - eng
GR  - 81971030/NSFC/
GR  - 82271461/NSFC/
GR  - 82201578/NSFC/
GR  - KJZD-K201900404/Chongqing Education Commission/
GR  - 2018YFC1314702/National Key R&D Program of China/
GR  - CYB19146/Postgraduate Research and Innovation Project of Chongqing/
PT  - Journal Article
DEP - 20240106
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - 0 (5' Untranslated Regions)
RN  - EC 2.1.2.1 (Glycine Hydroxymethyltransferase)
RN  - 0 (RNA, Messenger)
RN  - EC 2.1.2.- (Shmt2 protein, mouse)
RN  - EC 3.4.24.81 (Adam10 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - 5' Untranslated Regions
MH  - *Alzheimer Disease/genetics/metabolism
MH  - *Glycine Hydroxymethyltransferase/genetics
MH  - RNA, Messenger/genetics
PMC - PMC10953581
OTO - NOTNLM
OT  - 5'UTR
OT  - ADAM10
OT  - Alzheimer's disease
OT  - Kenpaullone
OT  - RNA binding protein
OT  - SHMT2
OT  - translation inhibitory element
COIS- The authors declare no conflict of interest.
EDAT- 2024/01/07 06:42
MHDA- 2024/03/21 12:44
PMCR- 2024/01/06
CRDT- 2024/01/06 09:57
PHST- 2023/11/27 00:00 [revised]
PHST- 2023/07/30 00:00 [received]
PHST- 2024/03/21 12:44 [medline]
PHST- 2024/01/07 06:42 [pubmed]
PHST- 2024/01/06 09:57 [entrez]
PHST- 2024/01/06 00:00 [pmc-release]
AID - ADVS7241 [pii]
AID - 10.1002/advs.202305260 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2024 Mar;11(11):e2305260. doi: 10.1002/advs.202305260. Epub 2024 
      Jan 6.