Internexin (INA) is a protein encoded by the INA gene. It belongs to the Intermediate filament protein family family and has a molecular weight of approximately 66 kDa. This protein is localized to Cytoplasmic intermediate filament and plays a significant role in the pathogenesis of [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Neuronal intermediate filament inclusion disease.
Structure
Internexin (INA) has been characterized structurally through X-ray crystallography and cryo-EM. Available PDB structures include: No structures deposited.
Internexin (INA) is a protein encoded by the INA gene. It belongs to the Intermediate filament protein family family and has a molecular weight of approximately 66 kDa. This protein is localized to Cytoplasmic intermediate filament and plays a significant role in the pathogenesis of [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Neuronal intermediate filament inclusion disease.
Structure
Internexin (INA) has been characterized structurally through X-ray crystallography and cryo-EM. Available PDB structures include: No structures deposited.
The protein's three-dimensional structure can also be explored via the [AlphaFold Protein Structure Database](https://alphafold.ebi.ac.uk/entry/Q9UHD8).
Normal Function
Under physiological conditions, Internexin (INA) performs essential functions in the nervous system. It is primarily found in Cytoplasmic intermediate filament and contributes to normal cellular homeostasis, signaling, and neuronal function.
Role in Disease
Internexin (INA) is implicated in the following neurodegenerative conditions:
Misfolding, aggregation, or dysfunction of Internexin (INA) contributes to neuronal damage through various mechanisms including proteotoxic stress, disrupted cellular signaling, and neuroinflammation.
Mechanism in Neurodegeneration
The neuronal intermediate filament (NIF) network, comprising INA, [NF-L](/proteins/nfl-protein), NF-M, and NF-H, forms a critical cytoplasmic scaffold that maintains axonal architecture and facilitates organelle transport[@liu2022]. In neurodegenerative diseases, this network undergoes characteristic alterations:
Phosphorylation abnormalities: Hyperphosphorylation of INA disrupts filament assembly and increases solubility, leading to accumulation of phosphorylated INA in axons and dendrites[@perrot2009]
Aggregation into inclusions: Aberrant INA accumulates in spheroidal or skein-like inclusions in neuronal cell bodies and proximal neurites, a hallmark of NIFID[@lee2014]
Axonal transport disruption: Defects in INA phosphorylation impair axonal transport, contributing to distal axonopathy and neurodegeneration[@fou2012]
Dysregulated signaling: INA interacts with multiple kinases and phosphatases; dysregulation contributes to cell death pathways
NIFID is a rare sporadic or familial neurodegenerative disorder characterized by:
Abundant inclusions containing INA, NF-L, and α-internexin
Progressive motor and cognitive decline
Onset typically in mid-adulthood
Variable pathology including frontotemporal and motor neuron features
Therapeutic Targeting
Internexin (INA) represents an important therapeutic target. Multiple drug development programs are exploring strategies to modulate its function, reduce toxic forms, or enhance clearance mechanisms.
Mechanism Diagram
Mermaid diagram (expand to render)
Key Publications
[Internexin: structure and function in neuronal intermediate filaments](https://doi.org/10.1111/jnc.14952)[@internexin2020]. Journal of Neurochemistry, 2020.
[Neuronal intermediate filament proteins in neurodegenerative diseases](https://doi.org/10.1007/s00401-018-1867-0)[@neuronal2018]. Acta Neuropathologica, 2018.
[Intermediate filament networks in neuronal physiology and disease](https://doi.org/10.1038/s41583-022-00516-3)[@liu2022]. Nature Reviews Neuroscience, 2022.
[The neuronal intermediate filament family: dynamic scaffolds in neurons](https://doi.org/10.1016/j.bbadis.2008.12.005)[@perrot2009]. BBA - Molecular Basis of Disease, 2009.