A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer's disease.

Epidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD).

Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.

Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation.

The regulatory region polymorphisms of the MTHFR gene are not associated with Alzheimer's disease.

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer's disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist.

p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y cells.

Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells.

[A case of acute cholinergic adverse effects induced by donepezil overdose: a follow-up of clinical course and plasma concentration of donepezil].

A 79-year-old woman with Alzheimer's disease was admitted due to acute cholinergic symptoms induced by overdose (45 mg) of donepezil (DPZ). Physical examination showed bradycardia, sinus arrhythmia, vomiting and respiratory insufficiency. She was treated with atropine intravenously and her cholinergic symptoms subsided in the next evening.

[A case report of syphilitic meningitis with right oculomotor nerve palsy].

A 63-year-old man presented with acute-onset right ptosis and diplopia. The patient reported having engaged in unspecified sexual activities during his third decade and was found to have positive syphilitic serological findings at the age of 56 years. No clinical symptoms were noted at this time.

PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells.

Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells.