mTOR signaling in proteostasis and its relevance to autism spectrum disorders

Judit Faus-Garriga; Isabel Novoa; Andrés Ozaita; Judit Faus-Garriga; Isabel Novoa; Andrés Ozaita

doi:10.3934/biophy.2017.1.63

AIMS Biophysics

2017, Volume 4, Issue 1: 63-89. doi: 10.3934/biophy.2017.1.63

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Review

mTOR signaling in proteostasis and its relevance to autism spectrum disorders

1.
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003, Barcelona, Spain
2.
Biobanco Hospital Universitari Vall d’Hebron (Biobanco HUVH), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, Spain

Received: 24 October 2016 Accepted: 12 January 2017 Published: 19 January 2017

Proteins are extremely labile cellular components, especially at physiological temperatures. The appropriate regulation of protein levels, or proteostasis, is essential for all cells. In the case of highly polarized cells like neurons, proteostasis is also crucial at synapses, where quick confined changes in protein composition occur to support synaptic activity and plasticity. The accurate regulation of those cellular processes controlling protein synthesis and degradation is necessary for proteostasis, and its deregulation has deleterious consequences in brain function. Alterations in those cellular mechanisms supporting synaptic protein homeostasis have been pinpointed in autism spectrum disorders such as tuberous sclerosis, neurofibromatosis 1, PTEN-related disorders, fragile X syndrome, MECP2 disorders and Angelman syndrome. Proteostasis alterations in these disorders share the alterations in mechanistic/mammalian target of rapamycin (mTOR) signaling pathway, an intracellular pathway with key synaptic roles. The aim of the present review is to describe the recent literature on the major cellular mechanisms involved in proteostasis regulation in the synaptic context, and its association with mTOR signaling deregulations in various autism spectrum disorders. Altogether, the cellular and molecular mechanisms in synaptic proteostasis could be the foundation for novel shared therapeutic strategies that would take advantage of targeting common disorder mechanisms.
- proteostasis,
- synaptic function,
- protein translation,
- protein degradation,
- autism spectrum disorders,
- mTOR signaling
Citation: Judit Faus-Garriga, Isabel Novoa, Andrés Ozaita. mTOR signaling in proteostasis and its relevance to autism spectrum disorders[J]. AIMS Biophysics, 2017, 4(1): 63-89. doi: 10.3934/biophy.2017.1.63

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Abstract

Proteins are extremely labile cellular components, especially at physiological temperatures. The appropriate regulation of protein levels, or proteostasis, is essential for all cells. In the case of highly polarized cells like neurons, proteostasis is also crucial at synapses, where quick confined changes in protein composition occur to support synaptic activity and plasticity. The accurate regulation of those cellular processes controlling protein synthesis and degradation is necessary for proteostasis, and its deregulation has deleterious consequences in brain function. Alterations in those cellular mechanisms supporting synaptic protein homeostasis have been pinpointed in autism spectrum disorders such as tuberous sclerosis, neurofibromatosis 1, PTEN-related disorders, fragile X syndrome, MECP2 disorders and Angelman syndrome. Proteostasis alterations in these disorders share the alterations in mechanistic/mammalian target of rapamycin (mTOR) signaling pathway, an intracellular pathway with key synaptic roles. The aim of the present review is to describe the recent literature on the major cellular mechanisms involved in proteostasis regulation in the synaptic context, and its association with mTOR signaling deregulations in various autism spectrum disorders. Altogether, the cellular and molecular mechanisms in synaptic proteostasis could be the foundation for novel shared therapeutic strategies that would take advantage of targeting common disorder mechanisms.

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