Abstract:
:Growing evidence suggests that decreased brain-derived neurotrophic factor (BDNF) levels are associated with Alzheimer's disease (AD) pathogenesis. Therefore, BDNF gene therapy is considered to be a promising therapeutic strategy for treating AD. Sendai virus (SeV) is a type I parainfluenza virus that does not interact with host chromosomes because of its strict cytoplasmic life cycle. Although SeV is nonpathogenic in primates, including humans, its infectivity for neurons is strong. Here we demonstrate that SeV vectors effectively infected neurons, even though they were injected into subcortical white matter. Moreover, SeV vectors significantly induced BDNF expression, ameliorating synaptic degeneration and memory deficits in a transgenic mouse model of AD (Tg2576). This is the first study to demonstrate that viral vector administration in white matter is sufficient to restore cognitive function in vivo. These results also support the feasibility of using SeV vectors for gene therapy targeting the brain.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Iwasaki Y,Negishi T,Inoue M,Tashiro T,Tabira T,Kimura Ndoi
10.1002/jnr.22830subject
Has Abstractpub_date
2012-05-01 00:00:00pages
981-9issue
5eissn
0360-4012issn
1097-4547journal_volume
90pub_type
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