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Oct 30, 2019

Seminar - Molecular mechanisms underlying memory functions and Alzheimer’s disease (Speaker: Dr. Florian Plattner)

Dr. Florian Plattner
Assistant Professor, Department of Psychiatry
University of Texas Southwestern Medical Center, USA

Date: Wednesday, 30-October-2019
Time: 2:30 p.m.
Venue: Seminar Room 1, G/F, Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Pokfulam, Hong Kong​

The first part of the talk will cover Dr. Plattner’s work into molecular mechanisms that can be targeted to boost memory performance. Memory enhancers are thought to be a valid treatment strategy for disorders with cognitive deficits, including Alzheimer’s disease (AD). Dr. Plattner’s research identified cyclin-dependent kinase 5 (Cdk5) and its activator p25 as important players in synaptic plasticity and memory functions. Dr. Plattner’s group found that p25 overexpression improved synaptic plasticity and enhanced spatial learning and memory. Based on these observations, Dr. Plattner’s group unraveled a novel mechanism, by which Cdk5 regulates the cell surface levels of the NMDA receptor subunit NR2B. Subsequently, Dr. Plattner’s group developed a small-interfering peptide (siP) that disrupts Cdk5-NR2B interaction, increases synaptic transmission and enhances memory. The characterization of this mechanism opens up new avenues for the development of novel treatment strategies for cognitive impairment.

The second part will cover Dr. Plattner’s research into the effect of ApoE4 on the regulation of surface receptor trafficking and its impact on synaptic plasticity. ApoE4 is the major genetic risk factor for sporadic late-onset AD. Individuals carrying one APOE4 allele are at ~3-fold increased risk of developing AD, and those carrying two APOE4 alleles are at more than 10-fold increased risk. Dr. Plattner’s research showed that ApoE4 induces trafficking deficits of a specific subset of neuronal cell surface receptors, thereby impairing synaptic plasticity. Specific inhibition of the sodium/hydrogen exchanger 6 (NHE6) attenuated these ApoE4-induced trafficking deficits and restored synaptic plasticity, suggesting that NHE6-related mechanisms may be targeted for the development of conceptually new therapeutic interventions for AD.