Synaptic defects associated with s-inclusion body myositis are prevented by copper
R Aldunate1, A N Minniti, D Rebolledo
1Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8370003, Santiago, Chile. raldunate@santotomas.cl
Summary
Copper treatment in a C. elegans model of sporadic inclusion body myositis (s-IBM) reduced toxic amyloid-beta oligomers. This improved neuromuscular function, suggesting oligomers drive s-IBM pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Gerontology
Background:
- Sporadic inclusion body myositis (s-IBM) is a degenerative muscle disorder in the elderly.
- s-IBM shares molecular pathology with Alzheimer's disease, notably amyloid-beta (Aβ) accumulation.
- The precise mechanisms and effective treatments for s-IBM remain elusive.
Purpose of the Study:
- To investigate Aβ-induced pathology in a C. elegans model of s-IBM.
- To evaluate the effects of copper on Aβ aggregation and neuromuscular function.
- To identify the toxic Aβ species responsible for neuromuscular dysfunction.
Main Methods:
- Utilized transgenic Caenorhabditis elegans expressing human Aβ peptide in muscle cells.
- Administered copper treatment to assess its impact on amyloid deposits and motility.
- Performed biochemical analyses and evaluated neuromuscular synaptic transmission and function.
Main Results:
- Copper treatment increased amyloid deposit size and number but reduced toxic Aβ-oligomers.
- Copper administration ameliorated motility impairments and improved neuromuscular synaptic structure and function.
- Aβ-oligomers were identified as the likely toxic species causing neuromuscular junction defects.
Conclusions:
- Aβ-oligomers are the primary drivers of neuromuscular junction dysfunction in s-IBM.
- Copper treatment shows therapeutic potential by reducing toxic Aβ species and restoring muscle function.
- C. elegans models are valuable for studying s-IBM pathogenesis and testing interventions.
More Related Videos
Related Concept Videos
01:22Lysosomal Hydrolases
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,...
01:26Chemical Synapses
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...
01:26Chemical Synapses
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...
01:20Sulfur Assimilation
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to become...
01:22Myasthenia Gravis ll: Pathophysiology
The disease process of myasthenia gravis begins at the neuromuscular junction, where antibodies attack key proteins needed for muscle activation. This immune reaction weakens signal transmission, leading to the characteristic muscle fatigue and weakness that define the condition.Immune-Mediated DamageIn most individuals, antibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane of muscle cells. By blocking acetylcholine binding, these antibodies prevent the nerve signal...
01:20Myasthenia Gravis: Overview and Treatment
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 leads...
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 leads...