PMID- 33511762
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220506
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 289
IP  - 8
DP  - 2022 Apr
TI  - Protein synthesis as a modifiable target for autism-related dendritic spine 
      pathophysiologies.
PG  - 2282-2300
LID - 10.1111/febs.15733 [doi]
AB  - Autism spectrum disorder (ASD) is increasingly recognized as a condition of 
      altered brain connectivity. As synapses are fundamental subcellular structures 
      for neuronal connectivity, synaptic pathophysiology has become one of central 
      themes in autism research. Reports disagree upon whether the density of dendritic 
      spines, namely excitatory synapses, is increased or decreased in ASD and whether 
      the protein synthesis that is critical for dendritic spine formation and function 
      is upregulated or downregulated. Here, we review recent evidence supporting a 
      subgroup of ASD models with decreased dendritic spine density (hereafter 
      ASD-DSD), including Nf1 and Vcp mutant mice. We discuss the relevance of 
      branched-chain amino acid (BCAA) insufficiency in relation to unmet protein 
      synthesis demand in ASD-DSD. In contrast to ASD-DSD, ASD models with hyperactive 
      mammalian target of rapamycin (mTOR) may represent the opposite end of the 
      disease spectrum, often characterized by increases in protein synthesis and 
      dendritic spine density (denoted ASD-ISD). Finally, we propose personalized 
      dietary leucine as a strategy tailored to balancing protein synthesis demand, 
      thereby ameliorating dendritic spine pathophysiologies and autism-related 
      phenotypes in susceptible patients, especially those with ASD-DSD.
CI  - (c) 2021 Federation of European Biochemical Societies.
FAU - Lu, Ming-Hsuan
AU  - Lu MH
AD  - Department of Medical Education, National Taiwan University Hospital, Taipei, 
      Taiwan, ROC.
FAU - Hsueh, Yi-Ping
AU  - Hsueh YP
AUID- ORCID: 0000-0002-0866-6275
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210222
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
SB  - IM
MH  - Animals
MH  - *Autism Spectrum Disorder/genetics/metabolism
MH  - *Autistic Disorder/genetics/metabolism
MH  - Dendritic Spines/genetics/metabolism
MH  - Humans
MH  - Mammals
MH  - Mice
MH  - Neurons/metabolism
MH  - Synapses/metabolism
OTO - NOTNLM
OT  - autism spectrum disorders
OT  - leucine
OT  - neurofibromatosis type I
OT  - synaptopathy
OT  - valosin-containing protein
EDAT- 2021/01/30 06:00
MHDA- 2022/04/21 06:00
CRDT- 2021/01/29 06:04
PHST- 2021/01/04 00:00 [revised]
PHST- 2020/10/27 00:00 [received]
PHST- 2021/01/26 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2021/01/29 06:04 [entrez]
AID - 10.1111/febs.15733 [doi]
PST - ppublish
SO  - FEBS J. 2022 Apr;289(8):2282-2300. doi: 10.1111/febs.15733. Epub 2021 Feb 22.