Vascular Dementia (VD) is a common
dementia disease after Alzheimer’s disease. It accounts for 1/5 of the dementia.
Similar to Japan, VD has a higher proportion in China than Alzheimer’s disease.
However, the pathogenesis of vascular dementia is still unclear. Cerebral blood
vessels lesions, caused by vascular risk factors, play an essential role in the
development of vascular dementia. Numerous researches show that reduced global
cerebral ischemia and reperfusion can lead to brain dysfunction and cognitive
decline. These conditions can obviously cause a shortage of brain energy
supply. And some metabolic syndromes like insulin resistance and dyslipidemia
are associated with lower cognitive performance. The insulin resistance is
relate to lower arterial blood flow and reduced cortical perfusion. Insulin
signal disorder can cause the reduction of energy substrate, such as ATP in the
brain. Recent reports have shown that improving the metabolism of ATP in the
brain may be a potential way to treat cerebral ischemic diseases.
As we all know, the tricarboxylic acid
cycle (TCA) is the main physiological process of ATP formation. When the body
is short of oxygen supply, the activity of this process weakens, resulting in
the decrease of ATP production, which hinders the normal function of brain.
Pyruvate dehydrogenase synthase (PDK) and Alpha Ketoglutaric Dehydrogenase (α-KGDHC)
are two key enzymes of aerobic oxidation of glucose. Under aerobic conditions,
pyruvic acid enters TCA cycle through the action of PDH. While α-KGDHC is the
key step to control the cycle smoothly. A recent research shows that regulation
of PDK1 can control the development of some risk factors of vascular dementia
such as hypertension, obesity, diabetes and stroke.
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