Molecular mechanisms of autism as a form of synaptic dysfunction
Autism spectrum disorders are a separate group of defects with a very high genetic component. Genetic screening has identified hundreds of mutations and other genetic variations associated with autism, and bioinformatic analysis of signaling pathways and gene networks has led to understanding that m...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2017-02-01
|
| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/878 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832575227603714048 |
|---|---|
| author | E. A. Trifonova T. M. Khlebodarova N. E. Gruntenko |
| author_facet | E. A. Trifonova T. M. Khlebodarova N. E. Gruntenko |
| author_sort | E. A. Trifonova |
| collection | DOAJ |
| description | Autism spectrum disorders are a separate group of defects with a very high genetic component. Genetic screening has identified hundreds of mutations and other genetic variations associated with autism, and bioinformatic analysis of signaling pathways and gene networks has led to understanding that many of these mutational changes are involved in the functioning of synapses. A synapse is a site of electrochemical communication between neurons and an essential subunit for learning and memory. Interneuronal communicative relationships are plastic. The most prominent forms of synaptic plasticity are accompanied by changes in protein biosynthesis, both in neuron body and in dendrites. Protein biosynthesis or translation is a carefully regulated process, with a central role played by mTOR (mammalian or mechanistic target of rapamycin). Normally mTOR-regulated translation is slightly inhibited, and in most cases mutational damage to at least one of the links of the mTOR signaling pathway, increases translation and leads to impaired synaptic plasticity and behavior. Deregulation of the local translation in dendrites is connected with the following monogenic autism spectrum disorders: neurofibromatosis type 1, Noonan syndrome, Costello syndrome, Cowden syndrome, tuberous sclerosis, fragile X chromosome, syndrome, and Rett syndrome. The review considers the most important mutations leading to monogenic autism, as well as the possibility of a mechanism-based treatment of certain disorders of the autism spectrum. |
| format | Article |
| id | doaj-art-5c885f32cc5f40a3beb5138d95e22e15 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2017-02-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-5c885f32cc5f40a3beb5138d95e22e152025-02-01T09:58:03ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592017-02-0120695996710.18699/VJ16.217565Molecular mechanisms of autism as a form of synaptic dysfunctionE. A. Trifonova0T. M. Khlebodarova1N. E. Gruntenko2Institute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASAutism spectrum disorders are a separate group of defects with a very high genetic component. Genetic screening has identified hundreds of mutations and other genetic variations associated with autism, and bioinformatic analysis of signaling pathways and gene networks has led to understanding that many of these mutational changes are involved in the functioning of synapses. A synapse is a site of electrochemical communication between neurons and an essential subunit for learning and memory. Interneuronal communicative relationships are plastic. The most prominent forms of synaptic plasticity are accompanied by changes in protein biosynthesis, both in neuron body and in dendrites. Protein biosynthesis or translation is a carefully regulated process, with a central role played by mTOR (mammalian or mechanistic target of rapamycin). Normally mTOR-regulated translation is slightly inhibited, and in most cases mutational damage to at least one of the links of the mTOR signaling pathway, increases translation and leads to impaired synaptic plasticity and behavior. Deregulation of the local translation in dendrites is connected with the following monogenic autism spectrum disorders: neurofibromatosis type 1, Noonan syndrome, Costello syndrome, Cowden syndrome, tuberous sclerosis, fragile X chromosome, syndrome, and Rett syndrome. The review considers the most important mutations leading to monogenic autism, as well as the possibility of a mechanism-based treatment of certain disorders of the autism spectrum.https://vavilov.elpub.ru/jour/article/view/878autism spectrum disorders (asd)the synapsemechanistic or mammalian target of rapamycin (mtor)mechanism-based therapysyndromic autism |
| spellingShingle | E. A. Trifonova T. M. Khlebodarova N. E. Gruntenko Molecular mechanisms of autism as a form of synaptic dysfunction Вавиловский журнал генетики и селекции autism spectrum disorders (asd) the synapse mechanistic or mammalian target of rapamycin (mtor) mechanism-based therapy syndromic autism |
| title | Molecular mechanisms of autism as a form of synaptic dysfunction |
| title_full | Molecular mechanisms of autism as a form of synaptic dysfunction |
| title_fullStr | Molecular mechanisms of autism as a form of synaptic dysfunction |
| title_full_unstemmed | Molecular mechanisms of autism as a form of synaptic dysfunction |
| title_short | Molecular mechanisms of autism as a form of synaptic dysfunction |
| title_sort | molecular mechanisms of autism as a form of synaptic dysfunction |
| topic | autism spectrum disorders (asd) the synapse mechanistic or mammalian target of rapamycin (mtor) mechanism-based therapy syndromic autism |
| url | https://vavilov.elpub.ru/jour/article/view/878 |
| work_keys_str_mv | AT eatrifonova molecularmechanismsofautismasaformofsynapticdysfunction AT tmkhlebodarova molecularmechanismsofautismasaformofsynapticdysfunction AT negruntenko molecularmechanismsofautismasaformofsynapticdysfunction |