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Metab Brain Dis. 2017 Aug;32(4):949-965. doi: 10.1007/s11011-017-0021-5. Epub 2017 Jun 3.

The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration.

Author information

1
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
2
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
3
Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
4
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
5
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.
6
Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.

Abstract

Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties. Despite the voluminous literature on the clinical advantages of 3-hydroxy-3-methylglutaryl Co-enzyme A reductase (HMGCR) inhibitors (statins) in cardiovascular system, the neuroprotective effects and the underlying mechanisms are little understood. Hence, the present review tries to provide a critical overview on the statin-induced neuroprotection, which are presumed to be associated with the ability to reduce cholesterol, Amyloid-β and apolipoprotein E (ApoE) levels, decrease reactive oxygen and nitrogen species (ROS and RNS) formation, inhibit excitotoxicity, modulate matrix metalloproteinases (MMPs), stimulate endothelial nitric oxide synthase (eNOS), and increase cerebral blood perfusion. This review is also aimed to illustrate that statins protect neurons against the neuro-inflammatory processes through balancing pro-inflammatory/anti-inflammatory cytokines. Ultimately, the beneficial role of statins in ameliorating the development of PD, AD, MS and cerebral ischemic stroke has been separately reviewed.

KEYWORDS:

3-hydroxy-3-methylglutaryl co-enzyme A reductase; Neurodegenerative diseases; Neuroprotection; Statins

PMID:
28578514
DOI:
10.1007/s11011-017-0021-5
[Indexed for MEDLINE]

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