Biography & Research:
Professor MSO at Technical University of Denmark 2016-now (Ph.D., Lund University 2004).
I am interested in the physical chemistry of neurodegenerative diseases.
Chem. Rev. 2012, 112, 5193: "Bioinorganic Chemistry of Alzheimer's Disease"
In this paper I synthesize a view of the biochemical basis of Alzheimer’s disease. It lists the evidence that metal ions calcium, iron, zinc and copper are central to Alzheimer’s disease. By combining data and observations, it is concluded that Abeta imbalance is regulated by such metal imbalances. I suggested that AD metal dyshomeostasis and conflicting data on metal levels in AD patients can be reconciled and described as a translocation of metal ions from bound pools in proteins to free pools that are chelatable and weakly bound (Threshold Kd = 10-6 M, the physical chemical threshold of non-specific binding). The mechanism (translocation of form rather than amount) explains the heterogenous metal data fairly well and also points a mixture of loss and gain of function mechanisms involved in the disease.
Progress in Neurobiology, 2016, 143, 36. "Alzheimer’s disease due to loss of function: A new synthesis of the available data"
Most theories today propose that Alzheimer is caused by toxic misfolded proteins (Abeta), but the toxic mode is not known; many proposals have been made, most notably perhaps that of membrane disruption by oligomers. Using the insight from our studies of energy in evolution and protein misfolding, this review paper synthesizes a disease mechanism of AD. It is shown that Abeta/APP is most likely a divalent metal transport system active in neuronal membranes, regulated by the secretases. Abeta is claimed to be a metal transport peptide, and this natural function explains why Abeta has a therapeutic window (beneficial in small amounts) as originally found by Yankner, and Smith and Perry among others.
In contrast to the presenilin hypothesis (e.g. Shen and Kelleher) this mechanism accounts also for the role of metal ions and Abeta in a complete but simple framework . For example, the reason why the toxic mode of the many different proteopathies has not been found is because it is a generic, systemic loss of functions of which the protein aggregation is a side effect.