The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer’s disease
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Alzheimer’s disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.
KeywordsAlzheimer’s disease Iron Radical Blood-brain barrier K16APoE HAYED peptide
This study was supported by the Public Welfare Technology Research Grant for Zhejiang Social Development [2015C33248], Natural Science Foundation of Zhejiang Province [Y17H160027], Open Object of the Key Laboratory of Shanghai Forensic Medicine [KF1606], Taizhou Science and Technology Program [1501KY32], Taizhou University Research Fund , Taizhou University Talent Fostering Fund [2015PY028], and Public Applied Technology Research Project of Zhejiang Province [2015C37081].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Gumienna-Kontecka E, Pyrkosz-Bulska M, (2014). Iron chelating strategies in systemic metal overload, neurodegeneration and cancer, Curr Med Chem. [Epub ahead of print].Google Scholar
- 6.Zou Z, Ma C, Zou R, Cheng L, Wang J, Zhi H, et al. Transitional metals distribution in tissues of transgenic Alzhemier’s disease model mice, and the involved roles of AD. Journal of Nanjing Agricultural University. 2007;30(2):116–21. ChineseGoogle Scholar
- 8.Kontoghiorghes GJ. New concepts of iron and aluminium chelation therapy with oral L1 (deferiprone) and other chelators. A Rev Anal. 1995;120:845–85.Google Scholar
- 9.McLachlan DR, Kruck TP, Lukiw WJ, Krishnan SS. Would decreased aluminum ingestion reduce the incidence of Alzheimer’s disease? CMAJ. 1991;145:793–804.Google Scholar
- 12.Bergeron RJ, Brittenham GM. The development of iron chelators for clinical use. CRC; Boca Raton, 1994, 353–371.Google Scholar
- 14.Levy M. Observational Study of Deferiprone (Ferriprox®) in the Treatment of Superficial Siderosis, https://clinicaltrials.gov/ct2/show/NCT01284127.
- 19.Gobinda S, Geoffry LC, Eric M, Teresa D, Thomas M, Wengenack, et al. A carrier for non-covalent delivery of functional Beta-galactosidase and antibodies against amyloid plaques and IgM to the brain. PLoS One. 2001;6(12):e28881.Google Scholar
- 22.Zlokovic BV, Jovanovic S, Miao W, Samara S, Verma S, Farrell CL. Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier. Endocrinology. 2000;141:1434–41.CrossRefGoogle Scholar
- 25.Bush AI. Metal complexing agents as therapies for Alzheimer’s disease. Trends in Neurobiol Aging. 2003;25:1031–8.Google Scholar