Close this search box.

Hermann Clemens Altmeppen, PhD

Grant Title: Enzymatic PrP shedding in humans: Biomarker potential and therapeutic target

Location: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Grant Year: 2022

Amounts of the cellular prion protein (PrPC) at the surface of neurons critically determine prion misfolding, neurotoxicity and drive progression in prion diseases. An enzyme or ‘molecular scissors‘ called ADAM10 continuously cleaves off a fraction of PrP molecules from the cells (‘shedding‘) in all of our brains and releases the protein into the extracellular space and body fluids. In this two-sided project we will investigate whether detection of this released (‘shed‘) PrP (e.g., in cerebrospinal fluid or blood samples) could serve as a biomarker for improved diagnostics and/or as a reliable read-out for any therapeutic strategies to reduce PrP levels in the brain (part I). In addition, we aim to identify ways and compounds to further stimulate the ADAM10-mediated shedding of PrP (part II), as we deem this process protective in at least two modes: (a) reduction of PrP (and, hence, misfolding and toxicity) at the cell surface; (b) production of soluble, shed PrP which may block and ‘detoxify‘ harmful prion seeds outside of the cells.

About the Researcher:

Hermann Clemens Altmeppen, PhD
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2002-2008: Studies of Human Biology/Biomedical Science at Philipps University Marburg, Germany (Diploma with main subjects ‘infection‘ and ‘cell biology‘; Diploma thesis on the proteolytic activation of a viral surface protein at the Institute of Virology, Marburg) with research internships at Med. Univ. Vienna (AT) and UC San Francisco (USA). 2009-2013: Dissertation project on proteolytic processing, prion protein biology and neurodegeneration at the Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (‘Dr. rer. nat.’ degree with distinction [summa cum laude] in 2013, Univ. Hamburg, Germany); 2013-2016: PostDoc; and subsequently Research Group Leader at aforementioned institution (Web: UKE – Neuropathology).

Besides various other aspects of prion protein biology, our research focusses on how endogenous proteolytic processing events on key proteins impact on fatal neurodegenerative diseases such as rare and transmissible prion diseases (e.g. Creutzfeldt-Jakob disease) or Alzheimer`s disease, the most frequent cause of dementia. We aim to translate these insights into novel diagnostic options and therapeutic approaches against these terrible and still incurable diseases.

Recipient of: