The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

Abstract

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

Does statin use affect amyloid beta deposition and brain metabolism?

“…Statins could significantly reduce depression and hospitalization in patients prone to psychiatric disorders 8 . Moreover, based on several studies, use of statin is correlated with less severe symptoms in patients with neurodegenerative diseases such as AD and Parkinson's disease (PD) 9 …”

“…8 Moreover, based on several studies, use of statin is correlated with less severe symptoms in patients with neurodegenerative diseases such as AD and Parkinson's disease (PD). 9 There have been reports on the probable effect of statins on future AD development. Recently, a meta-analysis conducted by Zhang et al concluded that statins, by inhibiting the formation of intracerebral amyloid, have a protective role against dementia and AD.…”

“… 8 Moreover, based on several studies, use of statin is correlated with less severe symptoms in patients with neurodegenerative diseases such as AD and Parkinson's disease (PD). 9 …”

Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study

“…As possible etiological factors of VaD are atherosclerotic vascular lesions, one of the important areas of treatment is lipid metabolism analysis and drug treatment for dyslipidemia [ 13 , 14 ]. Statins are regarded as the most common lipid-lowering drugs and are 3-hydroxy-3-methylglutaryl-coenzyme A reductase [HMG-CoA reductase (HMGCR)] inhibitors that are the rate-limiting enzymes in the mevalonate pathway [ 15 ].…”

Significance of dyslipidemia for primary open-angle glaucoma

“…Pleiotropic effects are therapeutic effects that are not related to the original main effect. For statins, mainly anti-inflammatory, immunomodulatory, and vascular endothelium-protective effects [25,29], as well as neuroprotective effects [30][31][32] have been demonstrated, which can also meaningfully intervene in the disease process in POAG. Experimentally, neuroprotective effects have been demonstrated in an OHT animal model [33].…”