4.5 Review

Sepiapterin reductase: Characteristics and role in diseases

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 17, Pages 9495-9506

Publisher

WILEY
DOI: 10.1111/jcmm.15608

Keywords

cancer; non-enzymatic activity; sepiapterin reductase; SPR deficiency; tetrahydrobiopterin

Funding

  1. National Key Research and Development Program of China [2017YFA0205200]
  2. National Natural Science Foundation of China [81773766, 81903845]
  3. Science and Technology Research Project of Hubei Provincial Department of Education [Q20192007]

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Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non-enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research.

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