A metabolic link between S-adenosylhomocysteine and polyunsaturated fatty acid metabolism in Alzheimer's disease.

There is evidence that vascular risk factors contribute to the pathology of Alzheimer's disease. Increased concentrations of circulating homocysteine are associated with vascular risk factors and Alzheimer's disease but the mechanisms involved are unclear. Homocysteine inhibits the hydrolysis of S-adenosylhomocysteine (SAH) which is a product inhibitor of S-adenosylmethionine (SAM) dependent methyltransferase reactions.

Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite.

Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T(H)1) cytokines.

Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice.

Parkinson's disease is a neurological disorder involving the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. There is increasing evidence that inflammation plays a role in the propagation of neurodegenerative processes in Parkinson's disease. We investigated the neuroprotective effects of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor with anti-inflammatory properties, in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Increased homocysteine and decreased adenosine formation in Alzheimer's disease.

Vascular risk factors increase the risk of Alzheimer's disease. Increased concentrations of circulating homocysteine are associated with vascular risk factors and Alzheimer's disease but the underlying mechanisms are unclear. Homocysteine inhibits the hydrolysis of S-adenosylhomocysteine leading to a decrease in the intracellular adenosine concentration.

Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression.

Background: (E)-4-Hydroxy-2-nonenal (HNE) is a highly electrophilic end-product of lipid peroxidation. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (NOS). ADMA is metabolised by dimethylarginine dimethylaminohydrolase (DDAH).

Homocysteine increases the production of asymmetric dimethylarginine in cultured neurons.

Increased circulating concentrations of homocysteine may be a risk factor for Alzheimer's disease and cognitive dysfunction in normal aging. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (NOS). ADMA is metabolized in neurons by the enzyme dimethylarginine dimethylaminohydrolase (DDAH).