Arundic Acid ameliorates cerebral amyloidosis and gliosis in Alzheimer transgenic mice.

Abstract

Like microglia, reactive astrocytes produce a myriad of neurotoxic substances in various brain pathologies, such as Alzheimer's disease (AD), trauma, and cerebral ischemia. Among the numerous products of reactive astrocytes, attention has recently been directed toward the possible detrimental role of S100B, because the protein has been shown to be highly expressed along with the progression of brain damage and to exert neurotoxic effects at high concentrations. The present study aimed to examine the possible role of astrocyte-derived S100B in the progression of cerebral amyloidosis and gliosis in transgenic mice overproducing mutant amyloid precursor protein (Tg APP(sw) mice, line 2576). For this purpose, arundic acid (Ono Pharmaceutical Co., Ltd., Mishima, Osaka, Japan), which is known to negatively regulate astrocyte synthesis of S100B, was orally administered to Tg APP(sw) mice for 6 months from 12 months of age, and the effects of the agent on the above parameters were examined. Here, we report that beta-amyloid deposits along with amyloid-beta peptide/S100B levels, as well as beta-amyloid plaque-associated reactive gliosis (astrocytosis and microgliosis), were significantly ameliorated in arundic acid-treated Tg APP(sw) mice relative to vehicle-treated Tg APP(sw) mice at 19 months of age. Based on the above results, arundic acid is considered to deserve further exploration as a promising therapeutic agent for AD.

• Authors: Takashi Mori, Terrence Town, Jun Tan, Nobumichi Yada, Yuko Horikoshi, Junki Yamamoto, Taiji Shimoda, Yoshihisa Kamanaka, Narito Tateishi, Takao Asano
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 318 Issue 2 Pg. 571-8 (Aug 2006) ISSN: 0022-3565 [Print] United States
• PMID: 16709678 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Caprylates
• Nerve Growth Factors
• ONO2506
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins
• S100B protein, human
• S100b protein, mouse

Topics

• Alzheimer Disease (drug therapy, genetics)
• Amyloid beta-Peptides (metabolism)
• Amyloidosis (drug therapy, genetics)
• Animals
• Astrocytes (drug effects)
• Blotting, Western
• Caprylates (therapeutic use)
• Enzyme-Linked Immunosorbent Assay
• Gliosis (drug therapy, genetics)
• Humans
• Image Processing, Computer-Assisted
• Immunohistochemistry
• Male
• Mice
• Mice, Transgenic
• Nerve Growth Factors (biosynthesis, genetics)
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins (biosynthesis, genetics)