# Functions of vitamin E and the tocopherol transfer protein

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $718,422

## Abstract

Alpha-tocopherol (vitamin E) is an essential nutrient and the major fat-soluble antioxidant in humans. The most critical health-promoting action of vitamin E is thought to be anchored in protecting the central nervous system (CNS) from damage to membranes, proteins and nucleic acids induced by reactive species or free radicals. The levels and distribution of vitamin E in the body are regulated by hepatic alpha tocopherol transfer protein (TTP), which regulates secretion of the vitamin from the liver to circulating lipoproteins, and in turn to all tissues. Accordingly, mutations in the TTPA gene are the only known cause for ataxia with vitamin E deficiency (AVED; OMIM 277460). Our studies over the years have identified critical functions and mechanisms of action of a-tocopherol and TTP and we have made important discoveries that detail how TTP transports the vitamin across cells in the liver and the cerebellum. The proposed research will focus on three areas of critical importance: 1) we will decipher the molecular mechanisms underlying TTP-facilitation of trafficking of a- tocopherol from the endocytic compartment to the plasma membrane. 2) We will examine the molecular mechanisms and physiological consequences of novel, antioxidant independent activities of vitamin E, and their consequences on neurological health in a mouse model of vitamin E deficiency. 3) We will decipher the mechanisms by which vitamin E prevents the pathological progression of non alcoholic fatty liver disease to severe, irreversible liver disease (non alcoholic steatohepatitis). The results from our studies will provide important new insight into the role of vitamin E in health and disease.

## Key facts

- **NIH application ID:** 10234935
- **Project number:** 1R01DK125115-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** DANNY MANOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $718,422
- **Award type:** 1
- **Project period:** 2021-04-20 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234935

## Citation

> US National Institutes of Health, RePORTER application 10234935, Functions of vitamin E and the tocopherol transfer protein (1R01DK125115-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10234935. Licensed CC0.

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