Msh2 — Muts Homolog 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Full Name | MutS Homolog 2 |
|---|---|
| Synonyms | MSH2, mutS homolog 2 |
| Chromosome | 2p16.3 |
| NCBI Gene ID | 4439 |
| OMIM | 604952 |
| Ensembl ID | ENSG00000116675 |
| UniProt ID | P43246 |
| Protein | [MSH2 Protein](/proteins/msh2-protein) |
| Associated Diseases | Lynch Syndrome, Alzheimer's Disease, Parkinson's Disease, ALS |
MSH2 (MutS Homolog 2) is a key DNA mismatch repair (MMR) gene that plays a critical role in maintaining genomic stability. The MSH2 protein forms heterodimers with MSH6 (MutSα) or MSH2-MSH3 (MutSβ) to recognize base-base mismatches and small insertion/deletion loops that arise during DNA replication. Beyond its canonical role in MMR, MSH2 has been implicated in neurodegenerative diseases through mechanisms involving DNA repair deficiency, somatic mutation accumulation, and altered cellular stress responses.
MSH2 is essential for the DNA mismatch repair system:
MSH2 is expressed in all brain cell types:
DNA damage accumulates in AD brains:
MSH2 involvement in PD:
While primarily a cancer predisposition syndrome:
| Approach | Mechanism | Status |
|---|---|---|
| Gene therapy | Restore MSH2 expression | Preclinical |
| Small molecules | Enhance MMR efficiency | Discovery |
| Antioxidants | Reduce oxidative DNA damage | Clinical trials |
The MSH2 protein functions as a core component of the mismatch repair (MMR) system, which corrects errors that escape the replication machinery's proofreading activity. MSH2 forms heterodimers with MSH6 (MutSα) and MSH3 (MutSβ) to recognize different types of mismatches.
Beyond mismatch repair, MSH2 participates in DNA damage response:
| Model | Phenotype | Key Findings |
|---|---|---|
| Msh2 knockout mice | Embryonic lethal | Essential for development |
| Conditional knockout | Tumor prone | Lymphomas, gastrointestinal cancers |
| Knock-in mutants | Variable | Hypomorphic alleles inform function |
The study of Msh2 — Muts Homolog 2 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] Edelmann W, et al. Cancer Res. 2000;60(4):983-989. PMID:10706125
[2] Yang J, et al. Nat Rev Cancer. 2021;21(10):645-661. PMID:34341578
[3] Shen J, et al. Nat Rev Neurosci. 2021;22(11):681-694. PMID:34663971
[4] Lovell MA, et al. J Neurosci Res. 2009;87(12):2776-2783. PMID:19462462
[5] Kennedy LJ, et al. Mutat Res. 2020;786-788:108318. PMID:32246918