Excerpted from an article available online:
Steven K Baker MD and Mark A. Tarnoplasky, MD PhD. Statin myopathies: phathophysiologic and clinical perspectives. Clin Invest Med 2001; 24(5): 258-72

Cholesterol biosynthesis and the isoprenoids:
The inhibition of HMG-CoA reductase by the HMGRIs
is approximately 14 steps and 9 to 10 enzymatic
reactions removed from the terminal step(s) in cholesterologenesis
Furthermore,
mevalonic acid, the immediate product of HMG-CoA
reductase, is a pivotal precursor intermediate which
gives rise to the vital isoprenoids en route to cholesterol.
It is not surprising, therefore, that inhibiting this
important biosynthetic pathway causes pleiotropic
metabolic consequences33,34 (Fig. 1).
Prenylation is a fundamental element of posttranscriptional
lipid modification of proteins and other
compounds and affects their function. Some of the
known isoprenoids include the following: (1)
isopentyladenosine, required for transfer RNA synthesis;
(2) dolichols, required for glycoprotein synthesis;
(3) heme A, a polyisoprenoid component of the electron
transport chain; and (4) ubiquinone, a polyisoprenylated
quinoid cofactor of the electron transport
chain, which accepts electrons from complexes I and
II.6,35,… It is estimated that
over 1% of mammalian cellular proteins are isoprenylated.
38 Isoprenylated proteins have been implicated in
smooth muscle cell migration and proliferation,33 and
skeletal muscle cell growth and differentiation.39–42
These conclusions were borne out of experiments in
which statin treatment impaired cell development in
culture, whereas the coapplication of mevalonate or
its distal metabolites (i.e., farnesol or geranylgeraniol)
reversed many of the inhibitory cellular effects of
statins.

in reference to #1--interference with tRNA--statins interfere with selenoprotein tRNA, and specifically decrease selenoprotein N. the glutathione peroxidase family, and the thioredoxin reductases, were recently identified as selenoproteins. theoretically, thru this action, statins could interfere with glutathione reductase activity which re-cycles glutathione within the brain--the major anti-oxidant within the brain.

in reference to #2--dolichols--the substantia nigra is composed largely of lipids. the Most abundant lipid comprising the Substantia Nigra is DOLICHOLS- accounting for up to 45% of the total amt of lipids within this structure.

# 3--decreasing heme A--recent evidence that reduced heme A is a pathologic finding in alzheimer's

statins also interfere with the funciton of lipid rafts --important functions of lipid rafts in refererence ot neuro system:

excerpted from "Membrane Lipid Rafts and their role in Axon Guidance. Guirland, C and Zheng, J Q.


"...Lipid rafts have recently received considerable attention because they are thought to be involved in many cellular functions, in particular, signal transduction for extracellular stimuli. Many of these functions
are also intimately related to the processes involved in neural development, including neurotrophic factor signaling and synaptic plasticity. Recent studies from our lab and others have indicated an important role for lipid rafts in axonal growth and guidance. Specifically, our data show that lipid rafts on the plasma membrane provide platforms for spatial and temporal
control of guidance signaling by extracellular cues..."