Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep15032
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Funding
- NSFC (the National Natural Science Foundation of China) [91132305, 81261120570]
- Hubei Provincial Natural Science Foundation [2014CFB221]
- Guangdong Provincial Natural Science Foundation [2014A030313715]
- Ministry of Science and Technology of China [2013DFG32670]
- Shenzhen Special Fund Project on Strategic Emerging Industry Development [JCYJ20130329103949650]
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Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models.
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