SYNGAP1: mind the GAP
A cardinal feature of early stages of human brain development centres on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopmen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-02-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00032/full |
| _version_ | 1819211296475709440 |
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| author | Nallathambi eJeyabalan James P Clement |
| author_facet | Nallathambi eJeyabalan James P Clement |
| author_sort | Nallathambi eJeyabalan |
| collection | DOAJ |
| description | A cardinal feature of early stages of human brain development centres on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein has been shown to cause Intellectual Disability with comorbid Autism Spectrum Disorder and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngap1 mouse models, have provided deeper insights into how downstream signalling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention. |
| first_indexed | 2024-12-23T06:24:49Z |
| format | Article |
| id | doaj.art-9ba5d78c7c194dc4821e0a16ad21f53b |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-23T06:24:49Z |
| publishDate | 2016-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-9ba5d78c7c194dc4821e0a16ad21f53b2022-12-21T17:57:05ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-02-011010.3389/fncel.2016.00032151587SYNGAP1: mind the GAPNallathambi eJeyabalan0James P Clement1Narayana Nethralaya FoundationJawaharlal Nehru Centre for Advanced Scientific ResearchA cardinal feature of early stages of human brain development centres on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein has been shown to cause Intellectual Disability with comorbid Autism Spectrum Disorder and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngap1 mouse models, have provided deeper insights into how downstream signalling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00032/fullIntellectual Disabilitysynaptic plasticityAutism Spectrum Disorderslearning and memoryNeurodevelopmental disordersSyngap1 |
| spellingShingle | Nallathambi eJeyabalan James P Clement SYNGAP1: mind the GAP Frontiers in Cellular Neuroscience Intellectual Disability synaptic plasticity Autism Spectrum Disorders learning and memory Neurodevelopmental disorders Syngap1 |
| title | SYNGAP1: mind the GAP |
| title_full | SYNGAP1: mind the GAP |
| title_fullStr | SYNGAP1: mind the GAP |
| title_full_unstemmed | SYNGAP1: mind the GAP |
| title_short | SYNGAP1: mind the GAP |
| title_sort | syngap1 mind the gap |
| topic | Intellectual Disability synaptic plasticity Autism Spectrum Disorders learning and memory Neurodevelopmental disorders Syngap1 |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00032/full |
| work_keys_str_mv | AT nallathambiejeyabalan syngap1mindthegap AT jamespclement syngap1mindthegap |