Lanosterol is a triterpenoid intermediate in the biosynthesis of cholesterol, which can induce the ubiquitination and degradation of HMG CoA reductase [1]. Defects in Lanosterol can lead to various diseases, including the formation of cataracts [2]. Lanosterol can inhibit the aggregation and toxicity of misfolded proteins related to neurodegenerative diseases [3].
In vitro, treatment with Lanosterol (5μM; 24h) significantly inhibited the cell death of dopaminergic neurons induced by 1-methyl-4-phenylpyridine (MPP+), increased autophagy in neurons, and induced uncoupling of mitochondria in neurons [4]. Treatment with Lanosterol (20μM; 48h) increased the endogenous level of 20S proteasome in A549 and Cos-7 cell lines, promoted proteasome degradation of misfolded proteins, and reduced the aggregation of mutant GFP-Δ9CAT protein [5].
In vivo, oral administration of Lanosterol (1 or 2%, w/w; 10 weeks) significantly inhibited the formation of abnormal crypts and multiple crypts in rat colon induced by nitrosomethane (AOM), and 2% Lanosterol significantly increased serum high-density lipoprotein and cholesterol levels [6]. Local ocular administration of Lanosterol (25mM; 6 weeks) improved the clarity of canine lenses and alleviated cataracts [7].
References:
[1] Chen N, et al. Biosynthetic Mechanism of Lanosterol: Cyclization. Angew Chem Int Ed Engl. 2015 Jul 20;54(30):8693-6.
[2] Zhao L, Chen X J, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts[J]. Nature, 2015, 523(7562): 607-611.
[3] Upadhyay A, Amanullah A, Mishra R, et al. Lanosterol suppresses the aggregation and cytotoxicity of misfolded proteins linked with neurodegenerative diseases[J]. Molecular neurobiology, 2018, 55(2): 1169-1182.
[4] Lim L, Jackson-Lewis V, Wong L C, et al. Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease[J]. Cell Death & Differentiation, 2012, 19(3): 416-427.
[5] Kinger S, Jagtap Y A, Dubey A R, et al. Lanosterol elevates cytoprotective response through induced-proteasomal degradation of aberrant proteins[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2024, 1871(2): 119631.
[6] Rao C V, Newmark H L, Reddy B S. Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis[J]. Cancer detection and prevention, 2002, 26(6): 419-425.
[7] Zhao L, Chen X J, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts[J]. Nature, 2015, 523(7562): 607-611.