This is us, Human Biology at RPTU
AG Human Biology
Our research focuses on the molecular basis of Alzheimer's disease (AD). The amyloid precursor protein, APP, plays a central role in AD.
We are interested in both the molecular mechanisms of its pathogenic function and its physiological function. The latter appears to be of particular importance, as there is increasing evidence that disturbances in the physiological function of APP lead to impaired morphology and defective transmission of neurotransmitters at the synapse.
The subcellular localization of APP and the APP homologous proteins APLP1 and APLP2 has a significant influence on their physiological function and pathogenic effect. Therefore, we are interested in the regulation of the subcellular anterograde and retrograde transport of APP.
Since nerve cells and especially their axons are very complex and cannot be renewed in the course of life, they represent the Achilles' heel of the brain and are very susceptible to changes in the course of ageing. Since the APP gene family also plays an important role in maintaining the axonal structure, this is another major research focus of our group.
To address these topics, we use a broad spectrum of classical and state-of-the-art structural biology, biochemical, cell biological and microscopic methods, which allow us to analyze the molecular processes of disease development in detail.
Alzheimer's Disease, APP function and transport
Molecular basis of Alzheimer's Disease: The pathological and physiological function of the APP gene family. Alzheimer's disease (AD) is the most common disease in elderly people. It is characterized by a progressive loss of cognitive functions, resulting in dementia. The cognitive decline is associated with the loss of neurons, reduced synaptic density, and two characteristic pathological hallmarks: neurofibrillary tangles containing the microtubule associated protein tau and extracellular plaques mainly composed of the ß-amyloid peptide (Aß) derived from the amyloid precursor protein (APP). APP is essential for normal synaptic function and its processing, which strongly depends on the intraneuronal localization, plays a major role in the etiopathology of AD.
Our research focuses on the neuronal function of the APP gene family and the molecular motor composition underlying its intracellular transport in neurons. Thereby we are mainly interested in changes of APP transport and function while aging and its consequences for AD.
Specifically our research is currently addressing the following aims, using proteomic, biochemical, immunocytochemical and video microscopic methods in different neuronal model systems:
- We determine the molecular basis of anterograde and retrograde transport of APP, whereby we investigate specifically the underlying motor composition and the influence of intracellular ligands as well as the influence of neuronal aging.
- We found that APP/APLPs function as cell adhesion molecules and investigate the resulting physiological and pathogenic consequences of APP/APLPs malfunction.
Thanks to the DFG, BioComp 3.0, DAAD, Klaus-Tschira Stiftung, Forschungskolleg Rheinland-Pfalz and Alzheimer Forschung Initiative (AFI) for funding our research.