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Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
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Cleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems.
Mehtap Bacioglu1, Manuel Schweighauser2, Derrick Gray3
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Acta Neuropathologica Communications
|June 17, 2024
Summary
Transmembrane protein 106B (TMEM106B) filaments form in the brain and spinal cord with age, appearing in astrocytes and non-neuronal cells. These amyloid inclusions are linked to neurodegeneration and cellular stress pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Filaments of transmembrane protein 106B (TMEM106B) form in an age-dependent manner.
- These filaments are found in both healthy individuals and those with neurodegenerative diseases.
- TMEM106B filament formation involves cleavage at residue 120, but the role of the C-terminal region is unclear.
Purpose of the Study:
- To investigate the structural details and cellular localization of TMEM106B filaments.
- To determine if TMEM106B inclusions are amyloid in nature.
- To explore the distribution of TMEM106B inclusions beyond the brain.
Main Methods:
- Antibody staining targeting the C-terminus of TMEM106B (residues 263-274).
- Staining with luminescent conjugated oligothiophenes to assess amyloid properties.
- In situ immunoelectron microscopy to visualize subcellular localization.
Main Results:
- Evidence suggests a second cleavage site in TMEM106B, potentially involving the C-terminal residues.
- TMEM106B inclusions were found in the dorsal root ganglia and spinal cord, primarily in non-neuronal cells.
- In the brain, TMEM106B inclusions were most abundant in astrocytes.
- TMEM106B inclusions exhibit amyloid characteristics and are often located within endosomal and lysosomal structures.
Conclusions:
- TMEM106B filament formation is a widespread phenomenon, extending beyond the brain to the spinal cord and peripheral nervous system.
- The presence of TMEM106B amyloid inclusions in astrocytes and their association with endolysosomal compartments suggest a role in cellular stress and neurodegenerative processes.
- Further research is needed to elucidate the precise function of TMEM106B cleavage and its C-terminal region in filament formation and disease pathology.
