Homocysteine (HC) may work inter alia as a Volume Transmission signal since HC is present in the brain and cerebrospinal fluid and binds to NMDA receptors. Furthermore, in cell cultures increased HC formation increases its export. In the present study we have shown that after intravenous injection in intact animals HC penetrates the blood-brain barrier. Hence, it works as a blood-born humoral signal. Furthermore, we have studied HC plasma levels in a group of Alzheimer's (AD) patients and compared with a group of age-matched patients. It has been confirmed that a positive correlation exists between age and HC plasma levels in the control group, but not in the AD patients. These results may depend on the fact that in AD patients high HC plasma levels (possibly associated with high glycine levels and/or excessive glutamate release) have favored neurodegeneration and, once this pathological process has been triggered off, the plasma HC levels become independent of the "physiological" aging-induced increase of HC plasma levels.
Homocysteine (HC) and dehydroepiandrosterone sulphate (DHEAS) plasma levels have been evaluated in groups of male and female patients with Parkinson's disease (PD) and in a group of female patients with Alzheimer's disease (AD) and compared with the corresponding plasma levels observed in a group of age-matched subjects. It has been confirmed that HC plasma levels are enhanced in both PD and AD patients. As far as the DHEAS plasma levels are concerned no changes have been observed in PD patients while a marked decrease has been observed in AD patients. These results support the view that while the pro-oxidant effects of HC and its agonist action at NMDA receptors can play a role in both neurodegenerative diseases, the role of DHEAS is more complex and may be an important factor only in certain neurodegenerative diseases. Thus, according to the present study DHEAS is likely to be involved in AD but not in PD.
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