Evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, may reduce the risk of Alzheimer's disease (AD). Statin action in patients with AD, as in those with heart disease, is likely to be at least partly independent of the effects of statins on cholesterol. Statins can alter cellular signaling and protein trafficking through inhibition of isoprenylation of Rho, Cdc42, and Rab family GTPases. The effects of statins on protein isoprenylation in vivo, particularly in the central nervous system, are poorly studied. We utilized two-dimensional gel electrophoresis approaches to directly monitor the levels of isoprenylated and non-isoprenylated forms of Rho, and Rab family GTPases.
Ostrowski SM, Johnson K, Siefert M, Shank S, Sironi L, Wolozin B, Landreth GE, Ziady AG. Simvastatin inhibits protein isoprenylation in the brain. Neuroscience 2016 May 12 [Epub ahead of print]