Elsevier

Molecular Aspects of Medicine

Volume 28, Issues 5–6, October–December 2007, Pages 591-606
Molecular Aspects of Medicine

Review
Vitamin E and neurodegenerative diseases

https://doi.org/10.1016/j.mam.2007.01.004Get rights and content

Abstract

Vitamin E is essential for neurological function. This fact, together with a growing body of evidence indicating that neurodegenerative processes are associated with oxidative stress, lead to the convincing idea that several neurological disorders may be prevented and/or cured by the antioxidant properties of vitamin E.

In this review, some aspects related to the role of vitamin E against Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and ataxia with vitamin E deficiency will be presented.

Introduction

Neurodegenerative diseases are defined by the progressive loss of specific neuronal cell populations and are associated with protein aggregates. A growing body of evidence suggests that oxidative stress plays a key role in the pathophysiology of neurodegenerative disorders (Evans, 1993, Jenner, 1994, Knight, 1997). Reactive oxygen species (ROS), comprising superoxide anions, hydroxyradicals and hydrogen peroxide, are produced as a result of normal and aberrant cellular reactions (Coyle and Puttfarcken, 1993, Halliwell, 1992). ROS are known to cause cell damage by way of three main mechanisms: lipid peroxidation, protein oxidation and DNA oxidation. Therefore, cells have developed several defense and repair mechanisms to deal with oxidative stress: antioxidants represent the first line of defense and comprise enzymes such as superoxide dismutase, catalase, glutathione peroxidase and small molecules, as vitamins E and C, which are able to neutralise ROS and can be regenerated by the cellular antioxidant network (Halliwell, 1999). The role of vitamin E in the central nervous system (CNS) has not fully elucidated, but it acts protecting cell membranes from oxidative damage by neutralising the effects of peroxide and oxygen free radicals. In addition to its antioxidant properties, tocopherol can act as an anti-inflammatory agent, which may also be neuroprotective, and can regulate specific enzymes, thus changing the properties of membranes (Martin et al., 1999).

Evidence suggests that the cellular free radical scavenger systems lose efficiency with aging and that the age-associated increase in oxidative stress plays a major role in neurodegenerative processes. The CNS is especially vulnerable to free radical damage because it has a high oxygen consumption rate, an abundant lipid content and a relative deficit in antioxidant systems, compared with other tissues (Coyle and Puttfarcken, 1993, Smith et al., 2000).

It is still unclear whether oxidative stress is the primary initiating event associated with neurodegeneration or a secondary effect related to other pathological pathways, but a growing body of evidence implicates it as being involved in the propagation of cellular injury (Jenner, 2003).

The appealing feature of the oxidative stress hypothesis for neurodegenerative diseases is that cumulative oxidative damage over time could account for the late life onset and the slowly progressive nature of these disorders. Since vitamin E is the only lipid-soluble, chain-breaking antioxidant in biological membranes (Burton et al., 1983, Ingold et al., 1987), it is reasonable to propose that vitamin E may play a role in the treatment of some of these diseases.

Although the consequences of oxidative damage have been implicated in many neurodegenerative disorders, this review will focus on Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and ataxia with vitamin E deficiency.

Section snippets

Alzheimer’s disease (AD)

AD is the most common neurodegenerative disease associated with aging; actually, it affects nearly 20–30 million people worldwide (Selkoe, 2005) and is present in almost half of individuals over the age of 85 (Puglielli et al., 2003). AD may have a genetic component (familial), where the onset of symptoms occurs relatively early in life (40s–50s); or may be sporadic (late-onset), where symptoms occur in individuals older than 60s (Law et al., 2001).

AD is clinically characterized by memory

Parkinson’s disease (PD)

PD is a chronic progressive neurodegenerative disease clinically characterized by bradykinesia, postural instability and tremor (Samii et al., 2004). Histopathologically, PD brains show intraneuronal deposition of alpha synuclein proteins (Lewy bodies) and irreversible loss of nigrostriatal dopaminergic neurons (Mark, 2001).

Amyotrophic lateral sclerosis (ALS)

ALS is a neurodegenerative disorder characterized by the selective death of upper and lower motor neurons, leading to profound muscle weakness and death, mostly by respiratory failure. The etiology of most ALS cases remains unknown, but 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1) (Rosen et al., 1993). The identification of sod1 (the gene encoding SOD1 protein) as a causative gene in ALS allowed the generation of multiple lines of transgenic mice, which exhibit a

Ataxia with vitamin E deficiency (AVED)

Mutations of the α-tocopherol transfer protein (α-TTP) gene, located on chromosome 8q, lead to reduced α-tocopherol concentrations in plasma and tissues, which lead ultimately to a severe syndrome named ataxia with vitamin E deficiency (AVED) (Ben Hamida et al., 1993). These patients show loss of neurons, symptoms of retinal atrophy, massive accumulation of lipofuscin in neurons including dorsal root ganglions, and retinitis pigmentosa (Yokota et al., 2000). The symptoms of AVED are similar to

Conclusion

Two relevant questions can be posed from this study. (1) What can be the basis for the contradictory results obtained by different clinical trials? (2) Should we abandon the idea that α-tocopherol may help protect against neurodegenerative diseases, or should we improve the trial conditions?

Although biochemical, cellular, and molecular biology data about α-tocopherol have increased dramatically, many molecular phenomena are still far from being fully elucidated.

The clinical intervention studies

Acknowledgements

Research in the authors’ laboratory is supported by grants from PRIN no. 2006065711_002.

References (111)

  • K.U. Ingold

    Vitamin E remains the major lipid-soluble, chain-breaking antioxidant in human plasma even in individuals suffering severe vitamin E deficiency

    Arch. Biochem. Biophys.

    (1987)
  • P. Jenner

    Oxidative damage in neurodegenerative disease

    Lancet

    (1994)
  • H.J. Kayden et al.

    Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans

    J. Lipid Res.

    (1993)
  • A. Kikuchi

    Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy

    Neurobiol. Dis.

    (2002)
  • M. Koenig et al.

    Deciphering the cause of Friedreich ataxia

    Curr. Opin. Neurobiol.

    (1997)
  • A. Law et al.

    Say NO to Alzheimer’s disease: the putative links between nitric oxide and dementia of the Alzheimer’s type

    Brain Res. Brain Res. Rev.

    (2001)
  • H.S. Lee et al.

    MPP(+) increases the vulnerability to oxidative stress rather than directly mediating oxidative damage in human neuroblastoma cells

    Exp. Neurol.

    (2000)
  • S.Z. Lei

    Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex

    Neuron

    (1992)
  • J. Li et al.

    Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation

    Biochem. Biophys. Res. Commun.

    (1997)
  • M.H. Mark

    Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration

    Neurol. Clin.

    (2001)
  • W.R. Markesbery

    Oxidative stress hypothesis in Alzheimer’s disease

    Free Radic. Biol. Med.

    (1997)
  • W.R. Markesbery et al.

    Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer’s disease

    Neurobiol. Aging

    (1998)
  • A. Martin et al.

    Effect of vitamin E intake on levels of vitamins E and C in the central nervous system and peripheral tissues: implications for health recommendations

    Brain Res.

    (1999)
  • T. Montiel et al.

    Role of oxidative stress on beta-amyloid neurotoxicity elicited during impairment of energy metabolism in the hippocampus: protection by antioxidants

    Exp. Neurol.

    (2006)
  • Y. Nishida

    Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse

    Biochem. Biophys. Res. Commun.

    (2006)
  • I.N. Odunze et al.

    MPTP toxicity in the mouse brain and vitamin E

    Neurosci. Lett.

    (1990)
  • T.L. Perry

    Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse

    Neurosci. Lett.

    (1985)
  • P. Rinaldi

    Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease

    Neurobiol. Aging

    (2003)
  • A. Samii et al.

    Parkinson’s disease

    Lancet

    (2004)
  • M.A. Smith et al.

    Oxidative stress in Alzheimer’s disease

    Biochim. Biophys. Acta

    (2000)
  • A. Stolzing et al.

    Tocopherol-mediated modulation of age-related changes in microglial cells: Turnover of extracellular oxidated protein material

    Free Radic. Biol. Med.

    (2006)
  • R.E. Tanzi et al.

    New frontiers in Alzheimer’s disease genetics

    Neuron

    (2001)
  • M.G. Traber

    Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism

    J. Lipid Res.

    (1992)
  • P.M. Abou-Sleiman et al.

    Expanding insights of mitochondrial dysfunction in Parkinson’s disease

    Nat. Rev. Neurosci.

    (2006)
  • J.D. Adams et al.

    Vitamin E uptake into the brain and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity

    J. Cereb. Blood Flow Metab.

    (1994)
  • Z.I. Alam

    A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease

    J. Neurochem.

    (1997)
  • A.C. Alonso et al.

    Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules

    Nat. Med.

    (1996)
  • A. Ascherio

    Vitamin E intake and risk of amyotrophic lateral sclerosis

    Ann. Neurol.

    (2005)
  • M.F. Beal

    Aging, energy, and oxidative stress in neurodegenerative diseases

    Ann. Neurol.

    (1995)
  • C. Ben Hamida

    Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping

    Nat. Genet.

    (1993)
  • C.I. Blake et al.

    Platelet mitochondrial respiratory chain function in Parkinson’s disease

    Mov. Disord.

    (1997)
  • E. Bossy-Wetzel et al.

    Molecular pathways to neurodegeneration

    Nat. Med.

    (2004)
  • L.I. Bruijn

    Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1

    Science

    (1998)
  • D.A. Butterfield et al.

    Vitamin E and neurodegenerative disorders associated with oxidative stress

    Nutr. Neurosci.

    (2002)
  • L. Canevari et al.

    Toxicity of amyloid beta peptide: tales of calcium, mitochondria, and oxidative stress

    Neurochem. Res.

    (2004)
  • A.M. Clement

    Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice

    Science

    (2003)
  • J.T. Coyle et al.

    Oxidative stress, glutamate, and neurodegenerative disorders

    Science

    (1993)
  • C. Desnuelle et al.

    A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group

    Amyotroph. Lateral Scler. Other Motor Neuron Disord.

    (2001)
  • D.T. Dexter

    Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease

    J. Neurochem.

    (1989)
  • D.T. Dexter

    Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study

    Mov. Disord.

    (1994)
  • Cited by (0)

    View full text