PMID- 36133808
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220924
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic 
      signaling through integrin receptors.
PG  - 934971
LID - 10.3389/fphar.2022.934971 [doi]
LID - 934971
AB  - Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the 
      pathological sequelae evolve from oligodendrocytes (OLs) within the central 
      nervous system and are targeted by the immune system, which causes widespread 
      white matter pathology and results in neuronal dysfunction and neurological 
      impairment. The progression of this disease is facilitated by a failure in 
      remyelination following chronic demyelination. One mediator of remyelination is 
      thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was 
      recently defined. MCT8 facilitates the entry of THs into oligodendrocyte 
      progenitor cell (OPC) and pre-myelinating oligodendrocytes (pre-OLs). Patients 
      with MS may exhibit downregulated MCT8 near inflammatory lesions, which 
      emphasizes an inhibition of TH signaling and subsequent downstream targeted 
      pathways such as phosphoinositide 3-kinase (PI3K)-Akt. However, the role of the 
      closely related mammalian target of rapamycin (mTOR) in pre-OLs during 
      neuroinflammation may also be central to the remyelination process and is 
      governed by various growth promoting signals. Recent research indicates that this 
      may be reliant on TH-dependent signaling through beta1-integrins. This review 
      identifies genomic and non-genomic signaling that is regulated through mTOR in 
      TH-responsive pre-OLs and mature OLs in mouse models of MS. This review critiques 
      data that implicates non-genomic Akt and mTOR signaling in response to 
      TH-dependent integrin receptor activation in pre-OLs. We have also examined 
      whether this can drive remyelination in the context of neuroinflammation and 
      associated sequelae. Importantly, we outline how novel therapeutic small 
      molecules are being designed to target integrin receptors on oligodendroglial 
      lineage cells and whether these are viable therapeutic options for future use in 
      clinical trials for MS.
CI  - Copyright (c) 2022 Emamnejad, Dass, Mahlis, Bozkurt, Ye, Pagnin, Theotokis, 
      Grigoriadis and Petratos.
FAU - Emamnejad, Rahimeh
AU  - Emamnejad R
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Dass, Mary
AU  - Dass M
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Mahlis, Michael
AU  - Mahlis M
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Bozkurt, Salome
AU  - Bozkurt S
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Ye, Sining
AU  - Ye S
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Pagnin, Maurice
AU  - Pagnin M
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
FAU - Theotokis, Paschalis
AU  - Theotokis P
AD  - B', Department of Neurology, Laboratory of Experimental Neurology and 
      Neuroimmunology, AHEPA University Hospital, Thessaloniki, Greece.
FAU - Grigoriadis, Nikolaos
AU  - Grigoriadis N
AD  - B', Department of Neurology, Laboratory of Experimental Neurology and 
      Neuroimmunology, AHEPA University Hospital, Thessaloniki, Greece.
FAU - Petratos, Steven
AU  - Petratos S
AD  - Department of Neuroscience, Central Clinical School, Monash University, Prahran, 
      VIC, Australia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220905
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9483185
OTO - NOTNLM
OT  - Akt
OT  - integrin
OT  - mTOR-mammalian target of rapamycin
OT  - monocarboxylate transporter 8 (MCT8)
OT  - oligodendrocyte (OL)
OT  - thyroid hormone
COIS- SP is the founder and Chief Scientific Officer of the start-up company NeuOrphan 
      Pty Ltd. (currently 50% shareholder) that will be commercializing the development 
      of DITPA-like molecules in collaboration with Monash University. The remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2022/09/23 06:00
MHDA- 2022/09/23 06:01
PMCR- 2022/09/05
CRDT- 2022/09/22 04:02
PHST- 2022/05/05 00:00 [received]
PHST- 2022/07/18 00:00 [accepted]
PHST- 2022/09/22 04:02 [entrez]
PHST- 2022/09/23 06:00 [pubmed]
PHST- 2022/09/23 06:01 [medline]
PHST- 2022/09/05 00:00 [pmc-release]
AID - 934971 [pii]
AID - 10.3389/fphar.2022.934971 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Sep 5;13:934971. doi: 10.3389/fphar.2022.934971. 
      eCollection 2022.