T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice.

Abstract

Tau pathology is implicated in mechanisms of neurodegenerative tauopathies, including Alzheimer's disease (AD) and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). It has been reported that transgenic mice expressing FTDP-17 mutation P301L of human tau (P301L mice) display extensive tau pathology and exhibit behavioral deficits with aging. In this study, we investigated the effects of T-817MA, a neuroprotective agent, on the motor and cognitive impairments associated with neuronal degeneration in P301L mice. T-817MA prevented the progression of motor deficit and the loss of spinal cord motor neurons in P301L mice. Furthermore, T-817MA significantly attenuated the spatial memory impairment and the reduction in synaptic terminal density in the hippocampal dentate gyrus of P301L mice. These results indicate that T-817MA improved the motor and cognitive impairments as a result of inhibiting neuronal degeneration derived from tau pathology in the P301L mice. Therefore, it is expected that T-817MA has a therapeutic potential for tau-related neurodegenerative diseases such as AD.

• Authors: Tetsuo Fukushima, Asako Nakamura, Noboru Iwakami, Yasushi Nakada, Hiroshi Hattori, Satoru Hoki, Hidetoshi Yamaguchi, Masaya Nakagawa, Nobuo Terashima, Hirokazu Narita
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 407 Issue 4 Pg. 730-4 (Apr 22 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21439944 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate
• Maleates
• Mapt protein, mouse
• Neuroprotective Agents
• Synaptophysin
• Thiophenes
• tau Proteins

Topics

• Alzheimer Disease (drug therapy, physiopathology)
• Animals
• Cognition Disorders (drug therapy, genetics, physiopathology)
• Hippocampus (drug effects, metabolism)
• Maleates (therapeutic use)
• Mice
• Mice, Transgenic
• Movement Disorders (drug therapy, genetics, physiopathology)
• Neuroprotective Agents (therapeutic use)
• Synaptophysin (metabolism)
• Thiophenes (therapeutic use)
• tau Proteins (genetics)