PMID- 24419271
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 231
IP  - 6
DP  - 2014 Mar
TI  - Neurobiology of autism gene products: towards pathogenesis and drug targets.
PG  - 1037-62
LID - 10.1007/s00213-013-3403-3 [doi]
AB  - RATIONALE: The genetic heterogeneity of autism spectrum disorders (ASDs) is 
      enormous, and the neurobiology of proteins encoded by genes associated with ASD 
      is very diverse. Revealing the mechanisms on which different neurobiological 
      pathways in ASD pathogenesis converge may lead to the identification of drug 
      targets. OBJECTIVE: The main objective is firstly to outline the main molecular 
      networks and neuronal mechanisms in which ASD gene products participate and 
      secondly to answer the question how these converge. Finally, we aim to pinpoint 
      drug targets within these mechanisms. METHOD: Literature review of the 
      neurobiological properties of ASD gene products with a special focus on the 
      developmental consequences of genetic defects and the possibility to reverse 
      these by genetic or pharmacological interventions. RESULTS: The regulation of 
      activity-dependent protein synthesis appears central in the pathogenesis of ASD. 
      Through sequential consequences for axodendritic function, neuronal disabilities 
      arise expressed as behavioral abnormalities and autistic symptoms in ASD 
      patients. Several known ASD gene products have their effect on this central 
      process by affecting protein synthesis intrinsically, e.g., through enhancing the 
      mammalian target of rapamycin (mTOR) signal transduction pathway or through 
      impairing synaptic function in general. These are interrelated processes and can 
      be targeted by compounds from various directions: inhibition of protein synthesis 
      through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation 
      of synaptic activity. CONCLUSIONS: ASD gene products may all feed into a central 
      process of translational control that is important for adequate glutamatergic 
      regulation of dendritic properties. This process can be modulated by available 
      compounds but may also be targeted by yet unexplored routes.
FAU - Kleijer, Kristel T E
AU  - Kleijer KT
AD  - Department Translational Neuroscience, Brain Center Rudolf Magnus, University 
      Medical Center Utrecht, Universiteitsweg 100, 3984 CG, Utrecht, The Netherlands.
FAU - Schmeisser, Michael J
AU  - Schmeisser MJ
FAU - Krueger, Dilja D
AU  - Krueger DD
FAU - Boeckers, Tobias M
AU  - Boeckers TM
FAU - Scheiffele, Peter
AU  - Scheiffele P
FAU - Bourgeron, Thomas
AU  - Bourgeron T
FAU - Brose, Nils
AU  - Brose N
FAU - Burbach, J Peter H
AU  - Burbach JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140114
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proteins)
SB  - IM
MH  - Animals
MH  - Child Development Disorders, Pervasive/drug therapy/*genetics/*metabolism
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Proteins/genetics/*metabolism
MH  - Signal Transduction/genetics
EDAT- 2014/01/15 06:00
MHDA- 2014/11/13 06:00
CRDT- 2014/01/15 06:00
PHST- 2013/03/07 00:00 [received]
PHST- 2013/12/14 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
AID - 10.1007/s00213-013-3403-3 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2014 Mar;231(6):1037-62. doi: 
      10.1007/s00213-013-3403-3. Epub 2014 Jan 14.