title: SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer's disease induced by amyloid β and excitatory amino acids.
abstract: Basic fibroblast growth factor (bFGF/FGF-2) is known to possess neuroprotective and neurite outgrowth activity properties. In this study, the effects of a novel synthetic compound that mimics the neuroprotective properties of bFGF - SUN11602 - were examined in vitro and in vivo. SUN11602 promoted neurite outgrowth of primarily cultured rat hippocampal neurons. For the in vivo study, an Alzheimer's disease (AD) model with severe damage to the hippocampal tissue was constructed by injecting the hippocampi of rats with aggregated Aβ1-40, followed 48 h later by an injection of ibotenate [an agonist for N-methyl-d-aspartate (NMDA) receptor]. Oral administration of SUN11602 at the midpoint of Aβ1-40 and ibotenate injections attenuated short-term memory impairment in the Y-maze test, as well as spatial learning deficits in the water maze task. In addition, the SUN11602 treatment inhibited the increase of peripheral-type benzodiazepine-binding sites (PTBBS), which are a marker for gliosis. A negative correlation was found between PTBBS numbers and learning capacity in the water maze task. These results suggest that SUN111602 improved memory and learning deficits in the hippocampally lesioned rats by preventing neuronal death and/or promotion of neurite outgrowth. Taken together, these results indicate that SUN11602, a bFGF-like compound with neuroprotective and neurite outgrowth activity, may be beneficial for the treatment of progressive neurodegenerative diseases such as AD.
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ogino
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: murayama.norihito.rk@asubio.co.jp.
authors.forename: Norihito
authors.initials: N
authors.lastname: Murayama
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Noshita
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Takemoto
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toba
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Oka
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Narii
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects
chemical_list: C584014:4-((4-(((4-amino-2,3,5,6-tetramethylanilino)acetyl)(methyl)amino)-1-piperidinyl)methyl)benzamide; D016229:Amyloid beta-Peptides; D001549:Benzamides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010655:Phenylenediamines; C078592:amyloid beta-protein (1-40); D007051:Ibotenic Acid; D005346:Fibroblast Growth Factors
keywords: Learning capacity; Neurite outgrowth; Neuroprotection; SUN11602; Spatial learning; bFGF