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Edbauer Lab - Synaptic Dysfunction
miR-125b and miR-132 overexpression differentially affects dendritic spine morphology.
Alzheimer's disease (AD) is the most common form of dementia, affecting more than 20 million people worldwide. There is no cure and current treatments are only modestly effective. The disease is characterized by cortical deposition of Aβ and tau aggregates and progressive loss of neurons and synapses. Soluble Aβ oligomers severely impair synaptic plasticity, the cellular correlate of learning and memory. We aim to identify therapeutic targets for AD based on the molecular mechanisms of synaptic dysfunction using primary neuron culture and transgenic mice as a model system. Additionally, we are interested in the pathomechanisms leading to neurodegeneration in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Both diseases have recently been recognized as opposing ends of a continuous spectrum and share pathological features and genetic mutations.
The methods range from lentiviral manipulation in vitro and in vivo, siRNA-screening, confocal imaging, proteomic approaches to electrophysiology.
Some of the questions we address:
- The levels of several microRNAs (short RNA molecules that fine-tune gene expression) are altered in brains of sporadic AD patients. How do they contribute to AD pathogenesis?
- How do other epigenetic changes (e.g. histone modifications, DNA methylation) contribute to neurodegeneration?
- Neuronal death in AD is at least partly due to excessive NMDA receptor (NMDAR) activity in what is called glutamate excitotoxicity. How does Aβ affect NMDAR function and thus promote excitotoxicity in AD?
- Can reprogramming of primary patient cells (e.g. fibroblasts) to neurons be used to generate better in vitro models for neurodegenerative diseases?
Responsible for content: Dr. Dieter Edbauer