Henri Huttunen group


Research People Selected publications

 

Henri Huttunen, PhD
Docent in Neurobiology, Project leader
P.O. Box 56, FI-00014 University of Helsinki
Phone: 57616 (internal), +358 50 4151729
Email: henri.huttunen at helsinki.fi

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Alzheimer’s disease (AD), the most common form of dementia, is quickly becoming the most expensive disease of our times. It was recently estimated that the current annual worldwide expenditure for dementia care (~450 billion €) already equals 1% of global GDP. Currently, only symptomatic treatment options are available for AD. Although recent AD research has focused on how to reverse or delay the cerebral amyloid pathology, amyloid-based therapies have not translated well into humans. Thus, Alzheimer’s disease, particularly its sporadic late-onset form, needs to be approached from various perspectives.

The functionality of all cells depends critically on protein-protein interactions (PPI), particularly on the formation of multi-protein complexes. The traditional methods for studying PPIs rely on steady-state analysis of protein complexes that have been extracted from their native cellular environment. This is a significant shortcoming for functional studies. We use Protein-fragment Complementation Assays (PCA), a novel group of methods that allows studying dynamics of PPIs in live cells, to understand basic molecular mechanisms involved in pathophysiology of neurodegenerative diseases. Currently, our focus is on normal cellular regulation of β-amyloid precursor protein (APP) and microtubule-associated protein Tau, molecules that are involved in amyloid plaque and neurofibrillary pathologies in AD, respectively. Our technology platform allows various types of approaches, including mechanistic studies and screening of novel small-molecule modulators of PPIs.

Using the PCA technology, we have recently discovered a mechanism how GABAA receptor activity regulates Tau phosphorylation. GABAA receptor is a target of many psychoactive drugs, such as benzodiazepines, and we are now working to understand what is the role of Tau in these drug responses. In another project, we have revealed a novel mechanism how neuronal apoptosis is regulated by proprotein convertase PCSK9 and lipoprotein receptors ApoER2 and VLDL receptor. These findings are connected to neuronal cholesterol metabolism, an important player in both AD pathophysiology and neuronal plasticity.