Botulinum neurotoxin type A subtype 2 confers greater safety than subtype 1 in a rat Parkinson's disease model.
Botulinum neurotoxin type A (BoNT/A) cleaves SNAP-25 and interrupts the release of acetylcholine. We previously reported that BoNT/A subtype 2 (BoNT/A2) ameliorates pathologic behavior more effectively than subtype 1 (BoNT/A1) in a rat Parkinson's disease model. Here, we further show BoNT/A2 has fewer adverse effects than BoNT/A1. We first confirmed that intrastriatal treatments of both BoNT/As had no-effect on dopaminergic terminals in the striatum. SNAP-25 cleaved by BoNT/A2 was strictly localized to the striatum on the injected side; however, SNAP-25 cleaved by BoNT/A1 diffused contralaterally. Furthermore, treatment with BoNT/A1 caused a significant reduction in body weight, while BoNT/A2 treatment did not. These results suggest that BoNT/A2 is more beneficial for clinical application against Parkinson's disease than BoNT/A1.
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 598-8531, Japan.
Masanori
M
Itakura
Tomoko
T
Kohda
Takeya
T
Kubo
Yuko
Y
Semi
Kazuhiro
K
Nishiyama
Yasu-Taka
YT
Azuma
Hidemitsu
H
Nakajima
Shunji
S
Kozaki
Tadayoshi
T
Takeuchi
D000818:Animals; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D059290:Dopaminergic Neurons / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D010300:Parkinson Disease / Q000188:drug therapy*; D059748:Proteolysis; D051381:Rats; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D015431:Weight Loss / Q000187:drug effects
D050825:Synaptosomal-Associated Protein 25; D019274:Botulinum Toxins, Type A