Related Experiment Video
Updated: Jun 2, 2025
06:56
Antibody Transfection into Neurons as a Tool to Study Disease Pathogenesis
Published on: September 26, 2012
10.7K
Impaired Presynaptic Function Contributes Significantly to the Pathology of Glycine Receptor Autoantibodies
Anna-Lena Wiessler1, Fang Zheng2, Christian Werner3
1Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University of Würzburg, Germany.
Neurology(R) Neuroimmunology & Neuroinflammation
|January 17, 2025
Summary
Autoantibodies against glycine receptors (GlyRs) can affect presynaptic function, impacting neurological conditions like stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). This study reveals GlyRα2 as a key presynaptic target, explaining diverse patient symptoms.
Area of Science:
- Neuroimmunology
- Synaptic Plasticity
- Autoimmune Neurological Disorders
Background:
- Autoantibodies (aAbs) targeting glycine receptors (GlyRs) are linked to stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM).
- Previous research focused on aAbs affecting postsynaptic GlyRs, but presynaptic effects remained unexplored.
- GlyR aAbs can bind to various GlyR α-subunits and occasionally the β-subunit.
Purpose of the Study:
- To investigate whether autoantibodies against GlyRs also impact the expression and function of presynaptic homomeric GlyRs.
- To determine the role of presynaptic GlyR autoantibodies in the pathophysiology of autoimmune neurological diseases.
Main Methods:
- Established interneuron cultures from mouse embryonic spinal cord neurons.
- Employed protein biochemistry and super-resolution microscopy to analyze aAb binding to presynaptic GlyRs.
- Utilized brainstem slice recordings to assess functional alterations in synaptic transmission.
Main Results:
- Exposure to GlyR aAbs did not alter the expression of proteins forming a functional glycinergic synapse, except for increased glycine transporter 2 (GlyT2) expression.
- Super-resolution microscopy showed patient-derived aAbs binding to both postsynaptic and presynaptic sites, with GlyRα2 identified as a predominant presynaptic GlyR subunit.
- Functional recordings demonstrated a significant reduction in inhibitory postsynaptic potential frequency due to presynaptic aAb binding.
Conclusions:
- This study provides the first evidence implicating presynaptic GlyR defects in the pathophysiology of autoimmune diseases like SPS and PERM.
- The diverse clinical manifestations and therapeutic responses in patients with GlyR autoimmunity are attributed to individually tuned binding preferences for presynaptic and postsynaptic targets.
- GlyRα2 is identified as a significant presynaptic target for autoantibodies in these neurological conditions.
More Related Videos
08:33Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
Published on: June 25, 2019
8.2K
10:19High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum
Published on: November 23, 2013
16.2K
Related Concept Videos
01:26Chemical Synapses
8.6K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
8.6K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.1K
01:20Myasthenia Gravis: Overview and Treatment
1.2K
Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
1.2K
01:05Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
03:03Amyloid Fibrils
9.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
01:22Lysosomal Hydrolases
3.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.7K