| Property | Value |
|---|---|
| Gene Symbol | IL24 |
| Full Name | Interleukin 24 |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 11009 |
| OMIM ID | 604136 |
| Ensembl ID | ENSG00000120289 |
| UniProt ID | Q13007 |
| Encoded Protein | Interleukin-24 (IL-24) |
| Associated Diseases | Alzheimer's disease, Parkinson's disease, cancer, inflammatory disorders |
IL24 (Interleukin-24) is a member of the IL-20 cytokine subfamily, which also includes IL-20, IL-22, and IL-26. Originally identified as a cytokine with tumor-suppressing properties, IL24 has emerged as a multifaceted cytokine with important functions in immune regulation, cell survival, and tissue homeostasis. Recent research has revealed that IL24 has significant roles in the central nervous system, where it modulates neuroinflammation, protects neurons from various insults, and may influence the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's disease[1][2].
The IL24 gene encodes a secreted protein of approximately 206 amino acids that signals through a heterodimeric receptor complex composed of IL-20R1 and IL-20R2. Alternative signaling through IL-22R1/IL-20R2 has also been described. These receptors are expressed in various tissues including brain, where they are found on neurons, astrocytes, microglia, and oligodendrocytes. The widespread distribution of IL24 receptors in the CNS suggests diverse functions beyond the immune system[3].
The IL24 gene is located on chromosome 1q32.2, a region that has been implicated in various autoimmune and inflammatory conditions. The gene consists of 5 exons spanning approximately 4.5 kb of genomic DNA. Several single nucleotide polymorphisms (SNPs) in the IL24 gene have been associated with:
IL24 is a secreted glycoprotein with the following features:
The protein adopts a typical four-helix bundle cytokine fold, with structural homology to other IL-10 family cytokines.
IL24 signals through two receptor complexes:
Type I receptor complex (IL-20R1/IL-20R2):
Type II receptor complex (IL-22R1/IL-20R2):
Signaling through these receptors activates:
IL24 is expressed in various neuronal populations within the CNS:
The effects of IL24 on neurons include:
IL24 has important paracrine effects on astrocytes:
Microglia, the resident immune cells of the brain, are major targets of IL24 action:
Anti-inflammatory effects: IL24 polarizes microglia toward an anti-inflammatory (M2-like) phenotype, characterized by:
Neuroprotection: M2-polarized microglia induced by IL24 secrete neurotrophic factors that support neuron survival. This includes increased BDNF and GDNF expression.
Spatial specificity: IL24 effects on microglia are spatially restricted, as the cytokine does not freely diffuse through tissue, allowing localized modulation of neuroinflammation[4][5].
Alzheimer's disease is characterized by chronic neuroinflammation, with activated microglia and astrocytes contributing to both plaque clearance and neuronal damage. IL24 has emerged as a key modulator of this process:
Microglial activation: In AD models, IL24 treatment reduces microglial activation as measured by:
Astrocyte response: IL24 modulates astrocyte reactivity around amyloid plaques:
IL24 influences amyloid pathology through multiple mechanisms:
The effects of IL24 on tau pathology include:
In mouse models of AD, IL24 administration (via viral vector or protein delivery) has been associated with:
These improvements correlate with reduced neuroinflammation and decreased amyloid burden in treated animals[6][7].
Parkinson's disease is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. IL24 has shown protective effects in multiple PD models:
MPTP toxicity: In mice treated with the dopaminergic neurotoxin MPTP, IL24 treatment:
α-Synuclein models: IL24 effects in α-synuclein transgenic models include:
Similar to its effects in AD, IL24 suppresses neuroinflammation in PD:
The neuroprotective effects of IL24 in PD involve:
These mechanisms converge to protect dopaminergic neurons from the various stresses present in PD pathophysiology[8][5:1].
| Cell Type | IL24 Expression | IL24R Expression |
|---|---|---|
| Neurons (hippocampus) | Low | High |
| Neurons (cortex) | Low | Moderate-High |
| Dopaminergic neurons | Low | High |
| Astrocytes | Moderate | High |
| Microglia | Low (resting), High (activated) | Moderate |
| Oligodendrocytes | Low | Low-Moderate |
IL24 expression is induced by:
Given its neuroprotective properties, IL24 is being explored as a therapeutic agent:
IL24 levels in cerebrospinal fluid (CSF) may serve as:
IL24-based therapeutics face several challenges:
Despite these challenges, IL24 remains a promising target for neurodegenerative disease therapy.
Sauane M, et al. IL-24: a unique cytokine with tumor-suppressing and wound-healing functions. Cytokine & Growth Factor Reviews. 2003. ↩︎
Poirier R, et al. IL-24 expression in the central nervous system and its role in neurological disorders. Journal of Neuroimmunology. 2019. ↩︎
Wang J, et al. The IL-20 cytokine family in neurodegeneration: a balancing act. Frontiers in Immunology. 2022. ↩︎
Khan N, et al. IL-24 modulates microglial activation and polarization in neurodegenerative diseases. Glia. 2021. ↩︎
Liu W, et al. IL-24 ameliorates Parkinson's disease pathology via suppression of neuroinflammation. Cellular and Molecular Neurobiology. 2023. ↩︎ ↩︎
Xie Q, et al. Interleukin-24 attenuates neuroinflammation and improves cognitive function in Alzheimer's disease models. Brain Behavior and Immunity. 2020. ↩︎
Zhang L, et al. Targeting IL-24 signaling as a novel therapeutic strategy for Alzheimer's disease. Neurobiology of Aging. 2024. ↩︎
Chen Y, et al. Interleukin-24 protects dopaminergic neurons against MPTP-induced toxicity. Cell Death & Disease. 2021. ↩︎