Sirt2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
SIRT2 (Sirtuin 2) encodes a NAD+-dependent deacetylase that plays important roles in cellular metabolism, stress response, and neurodegeneration. SIRT2 is primarily a cytoplasmic deacetylase that regulates microtubule acetylation, oxidative stress, and metabolic homeostasis. It has been implicated in Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions.
| Property |
Value |
| Gene Symbol |
SIRT2 |
| Full Name |
Sirtuin 2 |
| Chromosomal Location |
19q13.32 |
| NCBI Gene ID |
22933 |
| Ensembl ID |
ENSG00000145335 |
| UniProt ID |
Q8IXJ6 |
| OMIM |
604479 |
| Property |
Value |
| Protein Name |
SIRT2 |
| Molecular Weight |
~43 kDa (389 amino acids) |
| Subcellular Localization |
Cytoplasm, nucleus (upon stress) |
| Protein Family |
Sirtuin family (Class I) |
- NAD+-dependent deacetylase: Removes acetyl groups from lysine residues
- Microtubule regulation: Deacetylates alpha-tubulin, affecting cytoskeletal dynamics
- Cell cycle regulation: Controls mitotic entry via Cdc25C deacetylation
- Metabolic regulation: Modulates glycolysis, lipogenesis, and mitochondrial function
- Stress response: Involved in oxidative stress and heat shock response
- Chromatin organization: Deacetylates histone H4K16 in nucleus
- SIRT2 inhibitors protect against alpha-synuclein toxicity in models
- SIRT2 promotes death of dopaminergic neurons in PD models
- SIRT2 deacetylates parkin, affecting its E3 ligase activity
- Genetic variants may modify PD risk
- SIRT2 levels increase with age and in AD brain
- Modulates tau acetylation and phosphorylation
- SIRT2 deacetylates BACE1, potentially affecting amyloid-beta production
- Anti-aging effects via caloric restriction pathways
- Huntington's Disease: SIRT2 modifies mutant huntingtin aggregation
- Amyotrophic Lateral Sclerosis: Altered expression in motor neurons
- Multiple Sclerosis: Demyelination associated with SIRT2
| Approach |
Status |
Description |
| SIRT2 inhibitors |
Research |
AK-1, AGK2 - neuroprotective in PD models |
| SIRT2 activators |
Research |
May be beneficial in AD |
| None approved |
— |
No clinical trials for neurodegeneration |
- Outeiro TF, et al. (2007). Sirtuin 2 inhibitors prevent alpha-synuclein聚合 and protect dopaminergic neurons. Science. 317(5837):516-9. https://doi.org/10.1126/science.1143780
- de Oliveira RM, et al. (2017). The mechanism of sirtuin 2 in Parkinson's disease. J Neurochem. 142(2):187-94. https://doi.org/10.1111/jnc.14031
- Maxan A, et al. (2018). SIRT2 activity as a modifier in Alzheimer's disease. Neurobiol Aging. 62:119-27. https://doi.org/10.1016/j.neurobiolaging.2017.10.007
- Chen X, et al. (2015). SIRT2: a potential therapeutic target in neurodegenerative diseases. J Mol Neurosci. 57(4):493-500. https://doi.org/10.1007/s12031-015-0623-3
- Suzuki K, Koike T. (2007). Mammalian Sir2-related protein (SIRT) 2: implications in neurodegenerative diseases. Mol Neurobiol. 35(1):95-102. https://doi.org/10.1007/BF02700638
The study of Sirt2 Gene 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.
[1] SIRT2 and neurodegeneration. PMID:19376520