Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders.

Abstract

Vitamin E (alpha-tocopherol) is an essential nutrient and an important antioxidant. Its plasma levels are dependent upon oral intake, absorption and transfer of the vitamin to a circulating lipoprotein. The latter step is controlled by alpha-tocopherol transfer protein (alpha-TTP), which is a 278 amino acid protein encoded on chromosome 8, known to be synthesized in the liver. Mutations in alpha-TTP are associated with a neurological syndrome of spinocerebellar ataxia, called ataxia with vitamin E deficiency (AVED). Earlier studies suggested that alpha-TTP is found only in the liver. In order to establish whether alpha-TTP is expressed in the human brain, and what relationship this has to AVED, we studied immunohistochemically the presence of alpha-TTP in the brains of a patient with AVED, normal subjects, and patients with Alzheimer's disease (AD), Down's syndrome (DS), cholestatic liver disease (CLD) and abetalipoproteinemia (ABL). The neuropathology of both AD and DS is thought to be related in part to oxidative stress. The diseases of AVED, of cholestatic liver disease, and of abetalipoproteinemia are thought to be due to lack of circulating tocopherol, leading to inadequate protection against oxidative damage. We demonstrate the presence of alpha-TTP in cerebellar Purkinje cells in patients having vitamin E deficiency states or diseases associated with oxidative stress.

• Authors: R P Copp, T Wisniewski, F Hentati, A Larnaout, M Ben Hamida, H J Kayden
• Journal: Brain research (Brain Res) Vol. 822 Issue 1-2 Pg. 80-7 (Mar 20 1999) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10082886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1999 Elsevier Science B.V.

Chemical References

• Carrier Proteins
• alpha-tocopherol transfer protein

Topics

• Abetalipoproteinemia (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism)
• Ataxia (metabolism)
• Blotting, Western
• Brain Chemistry
• Carrier Proteins (analysis)
• Central Nervous System (cytology)
• Cholestasis (metabolism)
• Cytosol (chemistry, metabolism)
• Down Syndrome (metabolism)
• Female
• HeLa Cells
• Humans
• Immunohistochemistry
• Liver (cytology)
• Male
• Oxidative Stress (physiology)
• Purkinje Cells (chemistry, metabolism)
• Vitamin E Deficiency (metabolism)