F-SPONDIN GENE TRANSFER IMPROVES MEMORY PERFORMANCE AND REDUCES AMYLOID-beta LEVELS IN MICE

作者：Hafez D M; Huang J Y; Richardson J C; Masliah E; Peterson D A; Marr R A^*

来源：Neuroscience, 2012, 223: 465-472.

DOI：10.1016/j.neuroscience.2012.07.038

• F-spondin, reelin
• gene therapy
• amyloid-beta
• Alzheimer%26apos
• s disease

Alzheimer%26apos;s disease (AD) is the most prevalent form of dementia affecting the elderly. Evidence has emerged signifying that stimulation of the reelin pathway should promote neural plasticity and suppress molecular changes associated with AD, suggesting a potential therapeutic application to the disease. This was explored through the use of lentiviral vector-mediated overexpression of the reelin homolog, F-spondin, which is an activator of the reelin pathway. Intrahippocampal gene transfer of F-spondin improved spatial learning/memory in the Morris Water Maze and increased exploration of the novel object in the Novel Object Recognition test in wild-type mice. F-spondin overexpression also suppressed endogenous levels of amyloid beta (A beta(42)) in these mice and reduced At plaque deposition while improving synaptophysin expression in transgenic mouse models of AD. These data demonstrate pathologic and cognitive improvements in mice through F-spondin overexpression.

• 出版日期2012-10-25