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  • Review Article
  • Published:

PEDF: a multifaceted neurotrophic factor

Nature Reviews Neuroscience volume 4, pages 628–636 (2003)Cite this article

Key Points

  • Pigment epithelium-derived factor (PEDF) is a molecule with neurotrophic, neuroprotective and antiangiogenic properties. It is structurally related to the serpin family of serine proteases, and is widely expressed in the developing and adult nervous systems.

  • The structural domains that mediate the biological effects of PEDF have not been identified with precision. Similarly, its membrane receptor has not been isolated yet. However, its signal transduction pathway is better understood and seems to involve activation of nuclear factor κB, a transcription factor with numerous targets. In addition, PEDF signalling seems to involve several molecules that participate in apoptotic phenomena.

  • The neurotrophic effect of PEDF does not involve the stimulation of cell division, but of cell differentiation. Indeed, PEDF seems to control the transit of cells through the cell cycle, promoting their entry into a quiescent state. Its neuroprotective effect, which has been shown both in vivo and in vitro, seems to involve its ability to affect apoptotic pathways.

  • In addition to acting on neurons, PEDF can also affect the survival of other cells such as glia. More importantly, it is a potent antiangiogenic factor. This function has led to the suggestion that PEDF could be an effective antitumour agent.

  • The expression of PEDF seems to decline with age, and alterations on the availability of this factor might contribute to the development of different neurological conditions. It has therefore been proposed that PEDF might be an effective therapeutic agent for such conditions, but its potential has yet to be fulfilled.

Abstract

Pigment epithelium-derived factor (PEDF) is a potent and broadly acting neurotrophic factor that protects neurons in many regions of the central nervous system against insults such as glutamate excitotoxicity and oxidative damage. Since the crystal structure of PEDF was solved, its biological actions have begun to be mapped to specific structural domains. Here we discuss the structure and function of PEDF and the biochemical pathways it activates, and suggest ways in which this molecule might become a valuable therapeutic agent.

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Figure 1: Pigment epithelium-derived factor (PEDF) is expressed at multiple sites in the adult eye.
Figure 2: The brain distribution of pigment epithelium-derived factor (PEDF).
Figure 3: Stereoscopic model of pigment epithelium-derived factor derived from the crystal structure.
Figure 4: The transduction pathways activated by pigment epithelium-derived factor (PEDF).
Figure 5: Multiple effects of pigment epithelium-derived factor (PEDF) on neuroblastoma tumours.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, 64110, Missouri, USA

    Joyce Tombran-Tink

  2. Department of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, 06520, Connecticut, USA

    Colin J. Barnstable

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DATABASES

LocusLink

BDNF

CNTF

FGF

GDNF

IGF1

NF-κB

NGF

PEDF

VEGF

Glossary

VITREOUS

The transparent jelly that fills the posterior chamber of the eyeball.

EPENDYMAL CELLS

Epithelial cells within the brain parenchyma, which are in direct contact with the cerebrospinal fluid.

ALU REPEAT

A dispersed, repetitive DNA sequence found in the human genome in about 300,000 copies. It is named after the restriction endonuclease (AluI) that cleaves it.

RETINITIS PIGMENTOSA

An inherited condition of the retina, in which rods degenerate. The loss of rods diminishes the patient's ability to see in dim light and can also diminish peripheral vision.

LEBER'S CONGENITAL AMAUROSIS

Recessive eye condition that is characterized by the absence of rods and cones, and subsequent blindness.

MILLER–DIEKER SYNDROME

A form of lissencephaly that is accompanied by dysmorphic facial features.

LISSENCEPHALY

Literally meaning 'smooth brain', lissencephaly is a human brain disorder that is characterized by absence or reduction of the cerebral convolutions.

POLYMORPHISM

The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.

SERPINS

A family of inhibitors of serine proteinases. They are single-chain glycoproteins that have a highly ordered tertiary structure with a mobile reaction centre loop. Some members of this family are antithrombin III and plasminogen activator inhibitor 1.

GLAUCOMA

Eye disease that is characterized by an increase in intraocular pressure that causes changes in the optic disk and defects in the field of vision.

MÜLLER GLIA

The main glial cell type present in the retina. It is the only retinal glial cell that derives from retinal progenitor cells.

ADHERENS JUNCTION

A cell–cell junction also known as zonula adherens, which is characterized by the intracellular insertion of microfilaments. If intermediate filaments are inserted in lieu of microfilaments, the resulting junction is referred to as a desmosome.

CHOROID LAYER

The vascular layer of the eye. It also forms the ciliary body, which contains the muscles that control the size of the iris.

PANRETINAL LASER PHOTOCOAGULATION

Laser surgery that is performed on areas of the retina in which there is abnormal proliferation of blood vessels, trying to stop neovascularization.

AMYOTROPHIC LATERAL SCLEROSIS

A progressive neurological disease that is associated with the degeneration of central and spinal motor neurons. This neuron loss causes muscles to weaken and waste away, leading to paralysis.

CYCLINS

A family of proteins whose levels fluctuate throughout the cell cycle. By activating cyclin-dependent kinases, they help to regulate several stages of cell division.

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Tombran-Tink, J., Barnstable, C. PEDF: a multifaceted neurotrophic factor. Nat Rev Neurosci 4, 628–636 (2003). https://doi.org/10.1038/nrn1176

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