Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons

Martina Pigoni; Johanna Wanngren; Peer-Hendrik Kuhn; Kathryn M Munro; Jenny M Gunnersen; Hiroshi Takeshima; Regina Feederle; Iryna Voytyuk; Bart De Strooper; Mikail D Levasseur; Brian J Hrupka; Stephan A Mueller; Stefan F Lichtenthaler

Journal article

Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons

Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M Munro, Jenny M Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D Levasseur, Brian J Hrupka, Stephan A Mueller, Stefan F Lichtenthaler

MOLECULAR NEURODEGENERATION | BMC | Published : 2016

DOI: 10.1186/s13024-016-0134-z

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Abstract

BACKGROUND: The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the nervous system, such as in myelination and neuronal connectivity. Additionally, recent proteomic studies investigating BACE1 inhibition in cell lines and cultured murine neurons identified a wider range of neuronal membrane proteins as potential BACE1 substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L. METHODS AND RESULTS: We generated antibodies against SEZ6 and SEZ6L and validated these proteins as BACE1 substrates in vitro and in vivo. Levels of the sol..

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University of Melbourne Researchers

Jenny Gunnersen Author Anatomy and Physiology

Kathryn Munro Author Anatomy and Physiology

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Awarded by DFG

Awarded by Grants-in-Aid for Scientific Research

Funding Acknowledgements

We are grateful for financial support by the BMBF (JPND-RiModFTD), the Agency for Innovation by Science and Technology (IWT), the DFG (FOR2290), the Center of Excellence in Neurodegeneration CoEN), the Alzheimer Research Price of the Breuer Foundation, the Swedish Society of Medicine and the Swedish Society for Medical Research, the National Health and Medical Research Council (NHMRC) and the German Academic Exchange Service (DAAD).