Hyang-Sook Hoe, PhD
Primary tabs
JAD profile
Affiliation(s):
Korea Brain Reserach Institute (KBRI)
Areas of Interest:
APP, synapse, Alzheimer's disease
Biography & Research:
Alzheimer's disease (AD) is a neurodegenerative disease characterized by aggregated extracellular amyloid-β (Aβ) plaques in the brain. Extracellular Aβ deposition deteriorates axons, reduces dendritic spine density, and increases oxidative stress, partially by direct interaction between cellular enzymes and Aβ. Specifically, synapse formation and removal play important roles in learning and memory. Loss of synapses is the primary correlate of cognitive decline in AD. Synapses are affected by several molecules important in AD, including amyloid precursor protein (APP), which is a present at synapses. Many of the researchers have foucus on the effects of Abeta on synaptic function and its mechanisms of action. However, it is not well studied the normal function of APP at synapses.
Thus, our lab research is focused on the role of APP and its binding synaptic proteins (i.e., ApoE receptors) in the neuronal and synaptic damage that occurs with select neurodegenerative diseases of the central nervous system (CNS). Specifically, we will focus on examining A) the role of APP in synapse regulation in normal brain and in Alzheimer’s Disease (AD) and B) Novel treatments for AD including the effect of HDAC inhibitors and Abeta binding small molecules on Aβ levels and synaptic and cognitive function as well as its therapeutic effects on neurodegenerative disease.
To achieve long term objectives, a variety of techniques will be required. Additional assays of synaptic structure and function will be put into use in my laboratory. At present, we use conforcal microscopy and continuously collaborate closely with a laboratory having expertise in electrophysiology and drug discovery team at UCSD. In addition, tools will be developed to better examine human tissues, including those from patients with AD dementia, for evidence of APP and its binding partners mediated synaptic damage. Overall, the goal of our research is to identify the molecular mechanisms by which APP and its binding synaptic proteins regulate synapse and dendritic spine morphology, which will enhance our understanding of neuronal signaling, synaptic function, and neurodegenerative disorders. Moreover, our laboratory research will demonstrate the effectiveness of Aβ targeting small chemicals and novel HDAC inhibitors as effective novel therapeutic strategy for AD.
