The presynaptic protein ␣-synuclein, implicated in Parkinson disease (PD), binds phospholipids and has a role in brain fatty acid (FA) metabolism. In mice lacking ␣-synuclein (Snca ؊/؊ ), total brain steady-state mass of the mitochondria-specific phospholipid, cardiolipin, is reduced 22% and its acyl side chains show a 51% increase in saturated FAs and a 25% reduction in essential n-6, but not n-3, polyunsaturated FAs. Additionally, 23% reduction in phosphatidylglycerol content, the immediate biosynthetic precursor of cardiolipin, was observed without alterations in the content of other brain phospholipids. Consistent with these changes, more ordered lipid head group and acyl chain packing with enhanced rotational motion of diphenylhexatriene (DPH) about its long axis were demonstrated in time-resolved DPH fluorescence lifetime experiments. These abnormalities in mitochondrial membrane properties were associated with a 15% reduction in linked complex I/III activity of the electron transport chain, without reductions in mitochondrial number, complex II/III activity, or individual complex I, II, III, or IV activity. Reduced complex I activity is thought to be a critical factor in the development of PD. Thus, altered membrane composition and structure and impaired complex I/III function in Snca ؊/؊ brain suggest a relationship between ␣-synuclein's role in brain lipid metabolism, mitochondrial function, and PD.

The aims of this study were two-fold: (1) to improve our understanding of the thermal stability of per- and polyfluoroalkyl substances and (2) to investigate their decomposition mechanisms on spent granular activated carbon (GAC) during thermal reactivation. We studied seven perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkyl sulfonic acids (PFSAs), and one perfluoroalkyl ether carboxylic acid (PFECA) in different atmospheres (N2, O2, CO2, and air). The destabilization of studied compounds during thermal treatment followed first-order kinetics. The temperature needed for thermally destabilizing PFCAs increased with the number of perfluorinated carbons (n CF2). Decomposition of PFCAs such as perfluorooctanoic acid (PFOA) on GAC initiated at temperatures as low as 200 °C. The PFECA was even more readily decomposed than PFCA with the same n CF2. PFSAs such as perfluorooctanesulfonic acid (PFOS), on the other hand, required a much higher temperature (≥450 °C) to decompose. Volatile organofluorine species were the main thermal decomposition product of PFOA and PFOS at low to moderate temperatures (≤600 °C). Efficient mineralization to fluoride ions (>80%) of PFOA and PFOS on GAC occurred at 700 °C or higher, accompanied by near complete PFOA and PFOS decomposition (>99.9%). Thermal decomposition pathways of PFOA were proposed.

Alpha-synuclein is an abundant protein in the central nervous system that is associated with a number of neurodegenerative disorders, including Parkinson's disease. Its physiological function is poorly understood, although recently it was proposed to function as a fatty acid binding protein. To better define a role for alpha-synuclein in brain fatty acid uptake and metabolism, we infused awake, wild-type, or alpha-synuclein gene-ablated mice with [1-(14)C]palmitic acid (16:0) and assessed fatty acid uptake and turnover kinetics in brain phospholipids. Alpha-synuclein deficiency decreased brain 16:0 uptake 35% and reduced its targeting to the organic fraction. The incorporation coefficient for 16:0 entering the brain acyl-CoA pool was significantly decreased 36% in alpha-synuclein gene-ablated mice. Because incorporation coefficients alone are not predictive of fatty acid turnover in individual phospholipid classes, we calculated kinetic values for 16:0 entering brain phospholipid pools. Alpha-synuclein deficiency decreased the incorporation rate and fractional turnover of 16:0 in a number of phospholipid classes, but also increased the incorporation rate and fractional turnover of 16:0 in the choline glycerophospholipids. No differences in incorporation rate or turnover were observed in liver phospholipids, confirming that these changes in lipid metabolism were brain specific. Using titration microcalorimetry, we observed no binding of 16:0 or oleic acid to alpha-synuclein in vitro. Thus, alpha-synuclein has effects on 16:0 uptake and metabolism similar to those of an FABP, but unlike FABP, it does not directly bind 16:0; hence, the mechanism underlying these effects is different from that of a classical FABP.