Open AccessAn intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice
Author(s) -
Cheng YuSung,
Chen Zihten,
Liao TaiYan,
Lin Chen,
Shen Howard CH,
Wang YaHan,
Chang ChiWei,
Liu RenShyan,
Chen Rita PY,
Tu Panghsien
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606666
Subject(s) - nasal administration , genetically modified mouse , transgene , cognitive decline , peptide , drug , pharmacology , medicine , alzheimer's disease , biology , disease , dementia , biochemistry , gene
Alzheimer's disease ( AD ) is the most common neurodegenerative disease. Imbalance between the production and clearance of amyloid β (Aβ) peptides is considered to be the primary mechanism of AD pathogenesis. This amyloid hypothesis is supported by the recent success of the human anti‐amyloid antibody aducanumab, in clearing plaque and slowing clinical impairment in prodromal or mild patients in a phase Ib trial. Here, a peptide combining polyarginines (polyR) (for charge repulsion) and a segment derived from the core region of Aβ amyloid (for sequence recognition) was designed. The efficacy of the designed peptide, R 8 ‐Aβ(25–35), on amyloid reduction and the improvement of cognitive functions were evaluated using APP / PS 1 double transgenic mice. Daily intranasal administration of PEI ‐conjugated R 8 ‐Aβ(25–35) peptide significantly reduced Aβ amyloid accumulation and ameliorated the memory deficits of the transgenic mice. Intranasal administration is a feasible route for peptide delivery. The modular design combining polyR and aggregate‐forming segments produced a desirable therapeutic effect and could be easily adopted to design therapeutic peptides for other proteinaceous aggregate‐associated diseases.