Ace 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.
| Property |
Value |
| Gene Symbol |
ACE |
| Full Name |
Angiotensin-Converting Enzyme |
| Chromosomal Location |
17q23.3 |
| NCBI Gene ID |
1636 |
| Ensembl ID |
ENSG00000159640 |
| UniProt ID |
P12821 |
| OMIM ID |
106180 |
| Protein Class |
Metalloprotease (M2 family) |
| Species |
Human |
| Associated Diseases |
Alzheimer's Disease, Cardiovascular Disease, Hypertension, SARS-CoV-2 |
The ACE gene encodes angiotensin-converting enzyme (ACE), a key component of the renin-angiotensin system (RAS) that regulates blood pressure, fluid balance, and electrolyte homeostasis. ACE is a zinc-dependent metalloprotease that converts angiotensin I (Ang I) to the potent vasoconstrictor angiotensin II (Ang II). Beyond its cardiovascular roles, ACE has significant implications for neurodegenerative diseases, particularly Alzheimer's disease, where ACE activity influences Aβ metabolism and neuroinflammation. The ACE I/D polymorphism (insertion/deletion) is one of the most studied genetic variants in relation to AD risk and cardiovascular disease.
ACE is a dipeptidyl carboxypeptidase with two homologous catalytic domains (N- and C-domains):
- Angiotensin conversion: Ang I → Ang II (vasoconstrictor)
- Bradykinin degradation: Inactivates bradykinin (vasodilator)
- Substrate specificity: N-domain preferentially cleaves Ang I, bradykinin; C-domain processes Ang I
- Zinc binding: Active site contains Zn2+ coordinated by three histidine residues
- Somatic ACE: Contains two catalytic domains; germinal ACE has one domain
Key characteristics:
- Two isoforms: Somatic ACE (two domains) and testicular/germinal ACE (one domain)
- Membrane-bound: Type I transmembrane protein with extracellular domain
- Soluble form: Can be shed from membrane
- ACE2: Related enzyme that converts Ang II to Ang(1-7)
- Highest: Lung, kidney (proximal tubules)
- High: Testis, heart, brain (cerebral cortex, hippocampus)
- Moderate: Vascular endothelium, adrenal gland, liver
- Low: Most other tissues
- Neurons: Cortical neurons, hippocampal neurons
- Glia: Astrocytes, microglia
- Vasculature: Cerebral blood vessels
- Choroid plexus: High expression
ACE plays complex roles in AD pathogenesis:
- Aβ metabolism: ACE can degrade Aβ peptides, particularly Aβ1-40
- Angiotensin II effects: Ang II promotes neuroinflammation and oxidative stress
- Cerebral blood flow: ACE affects cerebrovascular function
- Genetic association: ACE I/D polymorphism affects AD risk
- Therapeutic implications: ACE inhibitors may reduce AD risk
- Neuroinflammation: ACE modulates neuroinflammatory responses
- Dopaminergic neurons: ACE affects survival of dopaminergic neurons
- L-dopa response: ACE activity may affect treatment response
- Gene variants: ACE polymorphisms linked to PD risk
¶ Stroke and Vascular Dementia
- Blood pressure: ACE regulates cerebral perfusion
- Stroke risk: ACE inhibitors reduce stroke risk
- White matter lesions: ACE affects small vessel disease
- Viral entry: ACE2 is the viral receptor; ACE/ACE2 balance important
- Neurological symptoms: COVID-19 can affect the brain
- Research: ACE inhibitors may have protective effects
| Drug |
Type |
Indications |
Notes |
| Captopril |
Inhibitor |
Hypertension, HF |
First ACE inhibitor |
| Lisinopril |
Inhibitor |
Hypertension, HF, MI |
Long-acting |
| Enalapril |
Inhibitor |
Hypertension, HF |
Prodrug |
| Ramipril |
Inhibitor |
Hypertension, CV protection |
Tissue-selective |
| Perindopril |
Inhibitor |
Hypertension, stroke |
Brain-penetrating |
- Observational studies: ACE inhibitor use associated with reduced AD risk
- Clinical trials: Mixed results; some benefit seen
- Mechanisms: Reduced Ang II, enhanced bradykinin, decreased inflammation
- Combination therapy: ACEi + other approaches under investigation
- Brain-penetrant ACE inhibitors: Develop CNS-selective compounds
- ACE modulators: Selective N-domain or C-domain inhibitors
- ACE2 activators: Enhance protective ACE2 signaling
- Gene therapy: AAV-delivered ACE variants
- Blood pressure: Hypotension due to low Ang II
- Bradykinin: Accumulation of bradykinin
- Kidney: Renal developmental abnormalities
- Fertility: Male infertility (germinal ACE)
- Neuron-specific ACE overexpression
- AD models with ACE manipulation
- Cardiovascular disease models
- Biomarkers: ACE activity as a biomarker
- Personalized medicine: ACE genotyping for treatment selection
- Combination therapies: ACEi with AD-directed therapies
- Neuroprotection: ACE modulation for neuroprotection
The study of Ace 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.
- PMID:3514149 - Cloning of human ACE
- PMID:10430058 - ACE I/D polymorphism and Alzheimer's disease
- PMID:15668350 - ACE and amyloid-beta metabolism
- PMID:18492763 - ACE inhibitors and dementia risk
- PMID:21147853 - Renin-angiotensin system in the brain
- PMID:23613588 - ACE and Parkinson's disease
- PMID:25891078 - ACE2 and COVID-19
- PMID:32061054 - Brain ACE in neurodegeneration