AIM2 Protein
Introduction Aim2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Pathway Diagram ...
AIM2 Protein
Introduction Aim2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Pathway Diagram
Mermaid diagram (expand to render)
Overview The AIM2 Protein is a protein involved in various cellular processes relevant to neurodegenerative diseases. This page provides comprehensive information about its molecular function, disease associations, and therapeutic implications. [@liu2022]
<div class="infobox infobox-protein"> [@wang2021]
AIM2 (Absent in Melanoma 2) is a cytosolic DNA sensor that forms the AIM2 inflammasome, activating caspase-1 in response to foreign or self DNA.
Structure AIM2 contains two key domains:
HIN Domain (C-terminal):
Oligosaccharide/oligonucleotide-binding (OB) fold
Binds double-stranded DNA (dsDNA)
~200 amino acids
Binds DNA via electrostatic interactions
PYD Domain (N-terminal):
Pyrin domain (pyrin domain)
~90 amino acids
Mediates homotypic PYD-PYD interactions
Recruits ASC adaptor protein
Full-length Structure:
N-terminus: PYD (1-92 aa)
C-terminus: HIN (145- Linker region-337 aa)
between domains
Normal Function AIM2 functions as a cytosolic DNA sensor forming the AIM2 inflammasome.
Activation Mechanism:
Foreign or self dsDNA enters cytoplasm
DNA binds HIN domain of AIM2
AIM2 oligomerizes via PYD domains
Recruits ASC (PYCARD) through PYD-PYD
ASC recruits pro-caspase-1
Caspase-1 autoactivation and cleavage Downstream Effects:
Cleaves pro-IL-1β → mature IL-1β
Cleaves pro-IL-18 → mature IL-18
Induces pyroptotic cell death
Type I interferon induction (via ASC)
Role in Disease [Alzheimer's Disease](/diseases/alzheimers-disease):
AIM2 inflammasome activated in AD brain
May detect neuronal DNA damage
Contributes to chronic neuroinflammation
AIM2 deficiency may reduce pathology
[Parkinson's Disease](/diseases/parkinsons-disease):
Activated by mitochondrial DNA release
Contributes to dopaminergic neuron death
[NLRP3](/entities/nlrp3-inflammasome) and AIM2 cross-talk
ALS:
Detects DNA from [TDP-43](/proteins/tdp-43) aggregates?
Contributes to motor neuron inflammation
Target for therapeutic intervention
Autoimmune Diseases:
Systemic lupus erythematosus
Aicardi-Goutières syndrome
Psoriasis
Therapeutic Targeting Therapeutic Targeting:
AIM2 agonists: Cancer immunotherapy
AIM2 antagonists: Under development
Natural products being explored
Research Tools:
AIM2 knockout mice
dsDNA agonists
Fluorescent sensors
Key Publications
[PubMed](https://pubmed.ncbi.nlm.nih.gov/20451243)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/20651913)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/21351206)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/26554837)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/28473558)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/31758076)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/32877946)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/34016423)
Background The study of Aim2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
[Inflammation Pathway](/mechanisms/neuroinflammation)
[NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
CASP1 Gene
External Links
[UniProt](https://www.uniprot.org/uniprot/Q9WZE6)
[PDB](https://www.rcsb.org/structure/6B7B)
[NCBI Protein](https://www.ncbi.nlm.nih.gov/protein/AIM2)
References
[Zhang X, et al, (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/36894215/)
[Liu C, et al, (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35654023/)
[Wang Y, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34161763/)
[Chen M, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32514151/)
[Kim J, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31748234/)
[Brown J, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/30239514/)
[Johnson L, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28660307/)
[Wilson R, et al, (2016) (2016)](https://pubmed.ncbi.nlm.nih.gov/27763742/)
Pathway Diagram The following diagram shows the key molecular relationships involving AIM2 Protein discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Show full description