IMR Press / FBL / Volume 10 / Issue 2 / DOI: 10.2741/1686

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The neuroprotective and angiogenesis inhibitory serpin, PEDF: new insights into phylogeny, function, and signaling
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1 Division of Pharmaceutical Sciences, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110, USA

Academic Editor: Philip Patston

Front. Biosci. (Landmark Ed) 2005, 10(2), 2131–2149; https://doi.org/10.2741/1686
Published: 1 September 2005
(This article belongs to the Special Issue Serpins in biology and medicine)
Abstract

Pigment Epithelial-Derived Factor (PEDF) is a non inhibitory serpin with neuroprotective and antiangiogenic actions. It is a potent and broadly acting neurotrophic factor that protects neurons from many regions of the CNS against a wide range of neurodegenerative insults including glutamate toxicity and oxidative stress. PEDF also functions as a natural inhibitor of angiogenesis, targeting the growth of only new vessels. The 50 kD protein is encoded by a single gene that shows strong conservation across phyla from fish to mammals. Two specific domains on the PEDF protein interact with extracellular matrix components and may mediate some of the biological actions of this protein. The transducers through which PEDF signals neurons and endothelial cells are defined and involves major pathways including Akt/NFkB , MAPK, and the caspases. PEDF is widely expressed in the nervous system and in most tissues of the body. A significant amount of the protein is found in the cerebral spinal fluid and circulating plasma as well. Therapeutic administration of the soluble protein or viral-mediated transfer of the gene in experimental in vivo models suggests that PEDF is an excellent pharmacological tool for slowing the progression of a range of neurodegenerative diseases and those pathologies associated with abnormal vessel growth in the eye and metastatic cancers of various tissues.

Keywords
Serpins
Phylogeny
RCL
Leader Sequence
Evolutionary Conservation
Chromosome Mapping
Nuclear Localization signal (NLS)
Angiogenesis
Neuroprotection
Signaling
VEGF
VEGFR2
FLK-1
NFkB
ERK1/2
MAP kinase
P38
Apoptosis
Review
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