| First Author | Lou G | Year | 2012 |
| Journal | Neuroscience | Volume | 223 |
| Pages | 225-37 | PubMed ID | 22885230 |
| Mgi Jnum | J:192491 | Mgi Id | MGI:5465247 |
| Doi | 10.1016/j.neuroscience.2012.08.003 | Citation | Lou G, et al. (2012) Intranasal administration of TAT-haFGF((1)(4)(-)(1)(5)(4)) attenuates disease progression in a mouse model of Alzheimer's disease. Neuroscience 223:225-37 |
| abstractText | Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 mug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress. |
