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Although amyotrophic lateral sclerosis (ALS) can be associated with cognitive impairment (ALSci) as a reflection of frontotemporal lobar degeneration, the basis of this process is unknown. The observation of neuronal and extraneuronal tau deposition in ALSci in addition to a unique tau phosphorylation at Thr175 has suggested that ALSci can be associated with alterations in tau metabolism. We have examined the association between phosphorylation at Thr175 and tau fibril formation. Both soluble and insoluble tau was purified from control, patients with Alzheimer’s disease (AD), ALS without cognitive impairment, and ALSci and the tendency to fibril formation assayed ex vivo using the thioflavin S fluorescence assay. The extent of fibril formation was significantly greater in tau derived from ALSci, with ALS‐derived tau being intermediate between control and AD‐derived tau. Using both Neuro2A and human embryonic kidney (HEK293T) cells, we expressed full‐length tau constructs harboring either a pseudophosphorylation at Thr175 (Thr175‐Asp‐tau), inhibition of Thr175 phosphorylation (Thr175‐Ala‐tau) or intact tau (wild‐type tau). Both tau fibril formation and cell death were significantly enhanced in the presence of Thr175‐Asp‐tau, regardless of the tau isoform, suggesting that phosphorylation of Thr175 is associated with tau fibril formation in ALSci.

Addition of cooper-monovalent-nicotinic acid complex to a synthetic medium specific for kojic acid production by Aspergillus flavus enhanced the production by about 47%. The substance is proposed to act via a biochemical utilization of the copper(I)-B3 complex in a manner similar to that of the naturally utilized nicotinic acid. NAD and NADP like carriers with higher reactivity have been predicted. According to this prediction the biosynthetic route of kojic acid has been interpreted on the basis of a model proposed by Bajpai et al. (1981). In this model the enzymes participating are dependent on NAD and NADP (glucose dehydrogenase and gluconate dehydrogenase) as well as on other reduction processes.

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