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Home » News and Events » National Eye Institute Symposium On Pigment Epithelium-Derived Factor (PEDF) » PEDF Rescues Adult Motor Neurons in a Model of Amyotrophic Lateral Sclerosis

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PEDF Rescues Adult Motor Neurons in a Model of Amyotrophic Lateral Sclerosis

Masako M. Bilak and Ralph W. Kunel

In amyotrophic lateral sclerosis (ALS), there is progressive destruction of motor neurons in the spinal cord, brainstem, and cerebral cortex. Pathogenesis of ALS may be multifactorial, involving incomplete synaptic clearance of glutamate leading to overactivation of glutamate receptors and subsequent cellular and DNA damage and oxidative stress. Neurotrophic factors are promising molecules that are capable of slowing dramatically, or even preventing, the progression of motor neuron degeneration in animal models of ALS. PEDF, a member of the serine protease inhibitor (serpin) family, has pleiotrophic activities as a survival factor for various types of neurons and as a potent antiangiogenic factor. PEDF is present in the spinal cord and in the cerebrospinal fluid, and its mRNA appears concentrated in neuronal cells, including the motor neuron. In our model of postnatal motor neuron degeneration, PEDF has significant neuroprotective effects against slow glutamate-mediated neurotoxicity. The effect is biologically important, producing significant sparing of gross organotypic morphology and preservation of motor neurons. The mechanisms by which PEDF protects motor neurons from degeneration are not clear. However, we have found that a small peptide fragment of the rhuPEDF molecule can be engineered to contain the complete motor neuron protective activity and that the neuroprotective action is likely to be mediated directly on motor neurons via a single class of PEDF receptor. PEDF may play important roles in providing significant neuroprotection of spinal motor neurons against acquired insults in postnatal life and may have pharmacotherapeutic potential as a neuroprotectant in motor neuron diseases such as ALS.



Department of Health and Human Services NIH, the National Institutes of Health USA.gov