Affiliations: Department of Neurology, Neuroregeneration Laboratory,
University of Jena Medical School, Jena, Germany
Note: [] Corresponding author: Christian Schmeer, PhD, University of Jena
Medical School, Department of Neurology, Erlanger Allee 101, D-07747 Jena,
Germany. Tel.: +49 3641 932 59 19; Fax: +49 3641 932 34 12; E-mail:
[email protected]
Abstract: Purpose: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors, or "statins", are used as cholesterol-lowering agents
worldwide. This review, focused on recent experimental and clinical data,
summarizes general mechanisms of statin actions underlying neuroprotective
effects in the central nervous system (CNS) and presents evidence for putative
mechanisms involving heat shock proteins and the survival-related PI-3K/Akt
pathway that may be beneficial for the treatment of neurological disorders.
Methods: We carried out a medline search on statin actions,
with respect to biochemical pathways and signal transduction on the one hand,
and clinical studies in neurologic and retinal diseases on the other hand.
Novel experimental data obtained in a rat model of axonal CNS injury were also
included. Results: Statins exert multiple effects on endothelial
function, cell proliferation, inflammatory response, immunological reactions,
platelet function, and lipid oxidation. These "pleiotropic actions" are
independent of cholesterol lowering and appear to be beneficial in the context
of brain injury. Several mechanisms of statin actions underlying
neuroprotective effects may also involve heat shock proteins and the
survival-related PI-3K/Akt pathway. Conclusions: Available data suggest that statins may be of
potential therapeutic use in a variety of diseases of the CNS including
ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of
retinal and eye diseases. Before general recommendations can be made and
specific therapeutic approaches can be developed, more reliable clinical data
and studies are required, and possible side effects must be carefully
evaluated.
