title: Intranasal administration of TAT-haFGF(₁₄₋₁₅₄) attenuates disease progression in a mouse model of Alzheimer's disease.
abstract: 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 μg/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 β-amyloid protein(1-42) (Aβ(1-42)) deposits as well as the levels of Aβ 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, Aβ pathology and oxidative stress.
authors.affiliation: Institute of Biomedicine, Jinan University, Guangzhou 510632, China.
authors.forename: G
authors.initials: G
authors.lastname: Lou
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Xiao
authors.forename: Q
authors.initials: Q
authors.lastname: Xiang
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D002795:Choline O-Acetyltransferase; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D057846:Cell-Penetrating Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016220:Fibroblast Growth Factor 1; D009569:Nitric Oxide; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005978:Glutathione; D000109:Acetylcholine