Startle Disease: New Molecular Insights into an Old Neurological Disorder

Natascha Schaefer; Robert J Harvey; Carmen Villmann

doi:10.1177/10738584221104724

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Startle Disease: New Molecular Insights into an Old Neurological Disorder

Journal article

Peer reviewed

Startle Disease: New Molecular Insights into an Old Neurological Disorder

Natascha Schaefer, Robert J Harvey and Carmen Villmann

The Neuroscientist, Vol.29(6), pp.767-781

2023

DOI: https://doi.org/10.1177/10738584221104724

PMID: 35754344

Appears in UniSC Diversity and Inclusion Research Collection

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Abstract

functional inhibition

glycine receptor

glycine transporter

maturation

protein-protein interactions

startle disease

trafficking

UniSC Diversity Area - Disability and Inclusion

Startle disease (SD) is characterized by enhanced startle responses, generalized muscle stiffness, unexpected falling, and fatal apnea episodes due to disturbed feedback inhibition in the spinal cord and brainstem of affected individuals. Mutations within the glycine receptor (GlyR) subunit and glycine transporter 2 (GlyT2) genes have been identified in individuals with SD. Impaired inhibitory neurotransmission in SD is due to pre- and/or postsynaptic GlyR or presynaptic GlyT2 dysfunctions. Previous research has focused on mutated GlyRs and GlyT2 that impair ion channel/transporter function or trafficking. With insights provided by recently solved cryo-electron microscopy and X-ray structures of GlyRs, a detailed picture of structural transitions important for receptor gating has emerged, allowing a deeper understanding of SD at the molecular level. Moreover, studies on novel SD mutations have demonstrated a higher complexity of SD, with identification of additional clinical signs and symptoms and interaction partners representing key players for fine-tuning synaptic processes. Although our knowledge has steadily improved during the last years, changes in synaptic localization and GlyR or GlyT2 homeostasis under disease conditions are not yet completely understood. Combined proteomics, interactomics, and high-resolution microscopy techniques are required to reveal alterations in receptor dynamics at the synaptic level under disease conditions.

Details

Title: Startle Disease: New Molecular Insights into an Old Neurological Disorder
Authors: Natascha Schaefer (Author) - University of Würzburg
Robert J Harvey (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Carmen Villmann (Author) - University of Würzburg
Publication details: The Neuroscientist, Vol.29(6), pp.767-781
Publisher: Sage Publications, Inc.
Date published: 2023
DOI: 10.1177/10738584221104724
ISSN: 1089-4098
PMID: 35754344
Organisation Unit: Centre for Bioinnovation; School of Health; School of Health and Behavioural Sciences - Legacy; University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99652298402621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Clinical Neurology; Neurosciences

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