| Gene |
[INA](/genes/ina) |
| UniProt |
Q16352 |
| PDB |
3TKN |
| Mol. Weight |
66 kDa |
| Localization |
Neuronal cytoplasm, axons, dendrites |
| Family |
Intermediate filament family |
| Diseases |
[Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/als), [Alzheimer's Disease](/diseases/alzheimers), [Infantile Neuroaxonal Dystrophy](/diseases/infantile-neuroaxonal-dystrophy) |
Alpha-Internexin (INA), also known as Internexin or Neurofilament-66 (NF-66), is a neuronal intermediate filament protein encoded by the INA gene on chromosome 10q24.3. Alpha-internexin is expressed primarily in the central nervous system, particularly in pyramidal neurons and certain populations of interneurons .
Alpha-internexin is unique among neuronal intermediate filaments as it is expressed during development before the other neurofilament subunits (NF-L, NF-M, NF-H) and may serve as a scaffold for their proper assembly. It is also a component of the characteristic inclusions found in several neurodegenerative diseases, including ALS and certain forms of dementia .
¶ Domain Structure
Alpha-internexin has the typical intermediate filament structure:
¶ Head Domain (1-82)
- N-terminal non-helical domain
- Contains regulatory sequences
- Phosphorylation sites for kinase regulation
¶ Rod Domain (83-418)
- Alpha-helical coiled-coil region
- Highly conserved across species
- Essential for dimer formation
- Contains the helix boundary motifs
¶ Tail Domain (419-556)
- C-terminal domain with multiple serine phosphorylation sites
- Projects from filament surface
- Regulates filament interactions
- Contains binding sites for associated proteins
- Expressed early in neuronal development
- Precedes expression of NF-L, NF-M, and NF-H
- May serve as nucleating scaffold for neurofilament assembly
- Essential for proper neuronal differentiation
- Forms homopolymers and heteropolymers
- Co-assembles with other intermediate filaments
- Provides structural stability to axons and dendrites
- Contributes to neuronal polarity
- Binds to other intermediate filament proteins
- Associates with synaptic proteins
- Links to microtubules via MAPs
- Interacts with signaling molecules
¶ Inclusion Body Formation
- Alpha-internexin is a component of:
- Bunina bodies in ALS
- Rosenthal fibers in astrocytomas
- Russell body inclusions
- Hyaline conglomerate inclusions
- CSF alpha-internexin elevated in ALS
- Detectable in blood with sensitive assays
- Potential biomarker for neuronal injury
- Correlates with disease progression
- Implicated in ALS pathogenesis
- Accumulation in PD brains
- Altered expression in AD
- Mutations cause hereditary spastic paraplegia
- Alpha-internexin as biomarker for ALS
- Monitoring disease progression
- Therapeutic response assessment
- Understanding inclusion formation mechanisms
- Developing neuroprotective strategies
- Gene therapy approaches
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Yuan et al., Alpha-internexin: structure and function (2006). Cell and Tissue Research. 2006;324(2):207-215.
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Bourrat et al., Alpha-internexin expression in neurological disorders (2015). Journal of Neuropathology and Experimental Neurology. 2015;74(5):410-426.
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Perrone et al., Alpha-internexin in ALS and related disorders (2007). Acta Neuropathologica. 2007;113(4):379-386.