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I. Alzheimer’s Disease Research (Makoto Michikawa, M.D., Professor)
The mechanism underlying the initiation of the clinico-pathological process in Alzheimer’s disease (AD) is assumed to be the age-related aggregation (oligomers) of amyloid β-protein (Aβ). Aβ is generated under physiological conditions; however, when it forms oligomers, they cause synaptic dysfunction and tauopathy. The modulation of Aβ metabolism could be therapeutic targets for AD.
The possession of apolipoprotein E (ApoE) epsilon 4 is a strong risk factor for the development of AD. ApoE is a key molecule that generates HDL in a brain, and HDL-cholesterol supply is crucial for maintenance neuronal morphology and its function. We found that ApoE3 has greater ability to generate HDL than ApoE4, which may result in earlier disruption of cholesterol metabolism in neurons and cause tauopathy.
II. Osteoporosis Resaearch (Sunao Takeshita, Ph. D., Associate Professor)
Bone is usually maintained on stiffness and elasticity by the bone remodeling of osteoblastic formation and osteoclastic resorption. The bone volume is constantly kept by its balance and diseases such as osteoporosis are caused of an imbalance between bone formation and resorption. The phenomenon of balanced bone metabolism is named “coupling” and a putative regulator, which is essential for this coupling, is so-called “coupling factor”. We are attempting to identify and clarify the molecular mechanisms of the factor.
We hypothesize that the coupling factor is produced by bone resorbing osteoclasts and stimulates bone formation. We recently identified a candidate for coupling factors by using DNA microarray and are characterizing this molecule both in vitro and in vivo. So far, all in vitro data indicate that this is corresponding to our criteria for coupling factors. Then, we decided to make transgenic and knockout mice and this is under investigation.
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