Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS

Woong Sun, Hiroshi Funakoshi, Toshikazu Nakamura

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motoneurons and degeneration of motor axons. We show that overexpression of hepatocyte growth factor (HGF) in the nervous system attenuates motoneuron death and axonal degeneration and prolongs the life span of transgenic mice overexpressing mutated Cu2+/Zn2+ superoxide dismutase 1. HGF prevented induction of caspase-1 and inducible nitric oxide synthase (iNOS) in motoneurons and retained the levels of the glial-specific glutamate transporter (excitatory amino acid transporter 2/glutamate transporter 1) in reactive astrocytes, We propose that HGF may be the first example of an endogenous growth factor that can alleviate the symptoms of ALS by direct neurotrophic activities on motoneurons and indirect activities on glial cells, presumably favoring a reduction in glutamatergic neurotoxicity.

Original languageEnglish
Pages (from-to)6537-6548
Number of pages12
JournalJournal of Neuroscience
Volume22
Issue number15
Publication statusPublished - 2002 Aug 1
Externally publishedYes

Fingerprint

Hepatocyte Growth Factor
Amyotrophic Lateral Sclerosis
Motor Neurons
Transgenic Mice
Disease Progression
Amino Acid Transport System X-AG
Neuroglia
Excitatory Amino Acid Transporter 2
Caspase 1
Nitric Oxide Synthase Type II
Astrocytes
Neurodegenerative Diseases
Nervous System
Axons
Intercellular Signaling Peptides and Proteins

Keywords

  • Amyotrophic lateral sclerosis
  • C-Met
  • Caspase-1
  • EAAT2
  • HGF
  • Motoneuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS. / Sun, Woong; Funakoshi, Hiroshi; Nakamura, Toshikazu.

In: Journal of Neuroscience, Vol. 22, No. 15, 01.08.2002, p. 6537-6548.

Research output: Contribution to journalArticle

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