title: Transforming growth factor-beta 2 causes an acute improvement in the motor performance of transgenic ALS mice.
abstract: Amyotrophic lateral sclerosis (ALS) is fatal disorder, characterized by the loss of motoneurons. The therapeutic potential of transforming growth factor-beta 2 (TGF-beta2) was examined using SOD1 mice. The SOD1 mice were treated with TGF-beta2 by repeated intraperitoneal injections. The highest dose of TGF-beta2 caused a rapid and marked improvement in the motor performance of the mice. This improvement lasted for between 2 and 3 weeks after which the TGF-beta2-treated mice rapidly deteriorated. At postmortem, the motoneurons in the TGF-beta2-treated SOD1 mice exhibited a large hypertrophy of their nucleoli, nuclei, and axons. In contrast, TGF-beta2 did not reverse the mitochondrial pathology. This may explain why the beneficial effects of TGF-beta2 and other growth factor on SOD1 mice are transient: TGF-beta2 is stimulating the motoneurons metabolic rate while one of their key metabolic organelles is damaged. Consequently, TGF-beta2 may be therapeutic for the forms ALS, with minimal mitochondrial involvement.
authors.affiliation: Neuromuscular Research Group, Department of Anatomy and Structural Biology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
authors.forename: W Antony
authors.initials: WA
authors.lastname: Day
authors.forename: Kyoko
authors.initials: K
authors.lastname: Koishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nukuda
authors.forename: Ian S
authors.initials: IS
authors.lastname: McLennan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2
chemical_list: C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2