Statins are often discussed in the
context of cardiovascular health, however this class of drugs fits neatly into
the world of neuroscience as well. These drugs are more formally known as HMG-CoA
reductase inhibitors, a name that describes their precise biological function
in the body. Statins inhibit the activity of the enzyme named HMG-CoA
reductase, which catalyzes the rate-limiting step in the synthesis of
cholesterol. Essentially, statins prevent the formation of mevalonate, a
necessary precursor of cholesterol. Thus, statins reduce cholesterol levels in
the body! This explains why they are often prescribed to those at risk for
cardiovascular disease; the hope is that lowering blood cholesterol levels will
prevent a heart attack or stroke.
Although statins directly affect a
process that occurs in the liver, these drugs have effects throughout the body,
including in neural tissue. Scientific
American recently published an article entitled “Do Statins Produced
Neurological Effects?” in which Dr. Beatrice Alexandra Golomb discusses how the
study of statins intersects with the field of neuroscience. Although the most
common side effects of this medication are muscle pain and fatigue, it has the
potential to cause adverse neurological effects. Dr. Golmb states that
“cognitive problems” such as memory loss or confusion are among the commonly
reported side effects of statins. Another potential consequence of statins is
“peripheral neuropathy” as a number of users report “burning, numbness, or
tingling in their extremities” (Golmb, 2017).
Some neurological effects of
statins are quite dependent on the “individual’s medical history” as well as
personal genetic and hormonal profiles (Golmb, 2017). Dr. Golmb demonstrates
this phenomenon using the example of aggression, a commonly studied subject
amongst neuropsychologists. She writes: “women taking statins, on average,
showed increased aggression; men typically showed less” (Golmb 2017). The
current hypothesis is that hormone levels modulate the effect of this medication.
Statins can also affect neurodegenerative disorders like “dementia, Parkinson’s
disease, or amyotrophic lateral schlerosis (ALS)” either by “triggering
symptoms” or by preventing their progression (Golmb, 2017). The possible
explanation Dr. Golmb presents for statins’ role in these disorders is that “statins
cause increases or decreases in tissue damage known as oxidative stress,” which
is a key player in neurodegenerative disease (Golmb, 2017). As Dr. Golmb
demonstrates, there are many interesting mechanisms by which statins can affect
healthy neural functioning.
 |
Fig. 1
There are many different
classes of statins, each with a unique molecular structure.
The structure of
lovastatin is shown above.
|
Statins were brought
to the attention of the Loyola Neuroscience community because of their
potential to reduce the severity of an autoimmune disorder that targets
peripheral nerves. This disease is called Guillain-Barré Syndrome (GBS) and it
is characterized by the immune system attacking and destroying the myelin on
peripheral nerves. In fact, GBS is the “leading cause of flaccid paralysis in
Western countries” and creates an estimated socioeconomic burden of over $1.7
billion per year (Langert, Goshu, & Stubbs, 2016). The research in the lab of Dr. Evan B.
Stubbs, which was presented to our Seminar by one of his colleagues, is focused
on the ability of a specific statin named lovastatin (see Figure 1) to
attenuate the progression of autoimmune neuritis. Their findings show that
administering lovastatin (cleverly encapsulated in biodegradable nanoparticles)
does significantly reduce the severity of autoimmune neuritis!
The
Stubbs Lab explains that the statins are effective when injected into the body
cavity because they “restrict the transendothelial trafficking of autoreactive
leukocytes” (Langert et al., 2016). Essentially, this means that lovastatin
prevents the inflammatory immune system agents from getting to the myelin, thus
protecting it.
It is very important to note that
using statins as a treatment for the paralysis that accompanies GBS is not
clinically viable. In the research presentation, these drawbacks were discussed
in detail. The necessary statin dosage to combat demyelination is ten times
greater than the current upper limit of statin prescriptions. Chronic use of
statins, especially at high dosages, is known to create problems in the long
term, specifically muscle weakness. This side effect can be explained by our
discussion of the function of statins; since they disrupt the synthesis of many
intermediates, they deplete isoprenoids and other compounds necessary for
continued muscle strength. Muscle weakness haunts the use of statins.
Although statins may not be the
most appropriate treatment for autoimmune demyelination, statins are still
salient in the world of neuroscience. Approximately “one in four Americans age
40 and older” are using statins (Golmb, 2017). As Dr. Golmb and Dr. Stubbs
highlight in their respective works, there remains much to be understood about
the ways in which such a commonly used drug affects our nerves, our brains, and
our bodies.
Works Cited
American
Heart Association. (n.d.). Cholesterol Medications. Retrieved December 13,
2017, from http://www.heart.org/HEARTORG/Conditions/Cholesterol/PreventionTreatmentofHighCholesterol/Cholesterol-Medications_UCM_305632_Article.jsp#.WjFiubbMx0s
Golmb,
B. A. (2017). Do Statins Produce Neurological Effects? Retrieved December 13,
2017, from
https://www.scientificamerican.com/article/do-statins-produce-neurological-effects/
Langert,
K. A., Goshu, B., & Stubbs, E. B. (2016). Attenuation of experimental
autoimmune neuritis with locally administered lovastatin-encapsulating
poly(lactic-co-glycolic) acid nanoparticles. Journal of
Neurochemistry,140(2), 334-346. doi:10.1111/jnc.13892
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