Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau.

Funder: Science and Technology Commission of Shanghai Municipality; FundRef: http://dx.doi.org/10.13039/501100003399Funder: Dr. John T. MacDonald Foundation; FundRef: http://dx.doi.org/10.13039/100010239Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration

Solubility of Multicomponent Systems in the Biodiesel Production by Transesterification of <i>Jatropha </i><i>c</i><i>urcas</i> L. Oil with Methanol

Biodiesel is manufactured by transesterification of animal fat or vegetable oil. The reactants (oil and methanol) and the products (fatty acid methyl ester and glycerol) are partially mutual soluble in the reaction process. Inter-solubility of the reaction components is essential data for the production design and process operation. In this work, the Jatropha curcas L. oil (oil) has been transesterified to give Jatropha curcas L. oil methyl ester (FAME). The inter-solubility of FAME + methanol + glycerol, oil + FAME + methanol, oil + glycerol + methanol, and oil + FAME + glycerol in the range from 298.15 K to 333.15 K has been conducted. Methanol is completely soluble in both FAME and glycerol but is not soluble in oil. With an increase in the mass fraction of FAME, the solubility of methanol in the oil + FAME phase increases. The transesterification reaction is carried out in the methanol phase, and as a result, the reaction shows an induction period. When FAME content increases to 70 %, the oil + methanol + FAME mixture becomes a homogeneous phase. Glycerol has a low solubility in both oil and FAME and, hence, is easily separated from the final product of biodiesel. The solubility is temperature insensible