Oxysterols, which are oxidized derivatives of cholesterol, play roles in lipid metabolism, inflammation, and cell signaling—but when dysregulated, they’re implicated in a variety of diseases.
🧬 Diseases & Disorders Associated with Oxysterols
🔹 1. Atherosclerosis & Cardiovascular Disease
- Oxysterols like 7-ketocholesterol and 25-hydroxycholesterol are found in oxidized LDL (oxLDL).
- Promote:
- Foam cell formation
- Endothelial dysfunction
- Inflammation in arterial walls
✅ Implication: Major contributors to plaque development and coronary artery disease.
🔹 2. Neurodegenerative Disorders
Oxysterols can cross the blood-brain barrier and affect neuronal health.
- 24(S)-hydroxycholesterol: Involved in brain cholesterol turnover
- Altered in Alzheimer’s disease
- 27-hydroxycholesterol: Linked to cognitive decline
- May promote amyloid-beta deposition and tau pathology
✅ Associated Conditions:
- Alzheimer’s disease
- Parkinson’s disease
- Multiple sclerosis
🔹 3. Inherited Metabolic Disorders
Mutations in enzymes that process oxysterols can cause severe syndromes.
- Cerebrotendinous xanthomatosis (CTX): Defect in CYP27A1 → accumulation of 27-hydroxycholesterol
- Smith-Lemli-Opitz Syndrome: Accumulation of toxic cholesterol precursors
- Niemann-Pick type C: Oxysterols used as diagnostic biomarkers
🔹 4. Cancer
Some oxysterols can promote or inhibit tumorigenesis depending on context.
- 27-hydroxycholesterol acts as a selective estrogen receptor modulator (SERM)
- Promotes ER-positive breast cancer growth
- Oxysterols may also influence:
- Tumor immune evasion
- Angiogenesis
- Metastasis
🔹 5. Immune Dysregulation
- 25-hydroxycholesterol: Involved in innate immunity
- Regulates interferon response
- Can have antiviral activity
- Chronic elevation may contribute to autoimmunity or inflammation
🧾 Summary Table
| Oxysterol | Associated Diseases/Disorders |
| 7-ketocholesterol | Atherosclerosis, inflammation, cytotoxicity |
| 25-hydroxycholesterol | Immune modulation, antiviral defense, autoimmune diseases |
| 24(S)-hydroxycholesterol | Alzheimer’s, neurodegeneration |
| 27-hydroxycholesterol | Atherosclerosis, breast cancer, Alzheimer’s |
| Accumulated oxysterols | CTX, Niemann-Pick C, Smith-Lemli-Opitz syndrome |