An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice. Issue 5 (29th March 2017)

• Record Type: Journal Article
• Authors: Cheng, Yu‐Sung; Chen, Zih‐ten; Liao, Tai‐Yan; Lin, Chen; Shen, Howard C‐H; Wang, Ya‐Han; Chang, Chi‐Wei; Liu, Ren‐Shyan; Chen, Rita P‐Y; Tu, Pang‐hsien
• Is Part Of: EMBO molecular medicine. Volume 9:Issue 5(2017)
• Page Start: 703
• Page End: 715
• Publication Date: 2017-03-29
• Subjects: Aβ -- Alzheimer disease -- peptide therapy -- polyarginine -- polyethylenimine; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.201606666
• Languages: English
• ISSNs: 1757-4676

Abstract

Abstract: 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, R8 ‐Aβ(25–35), on amyloid reduction and the improvement of cognitive functions were evaluated using APP/PS1 double transgenic mice. Daily intranasal administration of PEI‐conjugated R8 ‐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. Synopsis: Intranasal administration of an amyloid inhibitor peptide to Alzheimer transgenic mice reduces amyloid brain deposition in the brain and ameliorates cognitive decline. A peptide, R8 ‐Aβ(25–35), combining polyarginines (polyR) (for charge repulsion) and a segment derived from the core region of Aβ amyloid (for sequence recognition) was designed. Daily intranasal administration of the PEI‐conjugated R8 ‐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 could be easily extended to other proteinaceous aggregate‐associated diseases. Abstract : Intranasal administration of an amyloid inhibitor peptide to Alzheimer transgenic mice reduces amyloid brain deposition in the brain and ameliorates cognitive decline.