Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Synuclein (alphaS) is a 140-residue neuronal protein that forms insoluble cytoplasmic aggregates in Parkinson's disease (PD) and several other neurodegenerative disorders. Two missense mutations (A53T and A30P) are linked to rare forms of familial PD. The normal function of alphaS is unknown, and cultured cell systems that model its modification from soluble monomers to aggregated forms have not been reported. Through a systematic centrifugal fractionation of mesencephalic neuronal cell lines and transgenic mouse brains expressing wild-type or A53T human alphaS, we observed unusual, previously unrecognized species of alphaS that migrate well above the 17-kDa monomeric form in denaturing gels. Incubation at 65 degrees C of high-speed cytosols from cells or brains revealed a modified alphaS species migrating at approximately 36 kDa and an extensive higher molecular mass alphaS-reactive smear. Extraction of the cytosols with chloroform/methanol or with a resin (Lipidex 1000) that binds fatty acids resulted in a similar pattern of higher molecular mass alphaS forms. On the basis of this effect of delipidation, we reexamined the primary structure of alphaS and detected a motif at the N and C termini that is homologous to a fatty acid-binding protein signature. In accord, we found that purified human alphaS binds oleic acid, with an apparent K(d) of 12.5 microM. We also observed an enhanced association of A53T alphaS with microsomal membranes in both mesencephalic cells and transgenic mouse brains. We conclude that alphaS has biochemical properties and a structural motif that suggest it is a novel member of the fatty acid-binding protein family and may thus transport fatty acids between the aqueous and membrane phospholipid compartments of the neuronal cytoplasm.
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PMID:alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. 1148 78

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. alpha-Syn has biochemical properties and a structural motif characteristic of fatty acid binding proteins. Using the fatty acid binding resin Lipidex-1000, we investigated the capture of alpha-, beta-, and gamma-syn proteins as lipid-associated proteins from normal and DLB brain lysates, and from normal human cerebrospinal fluid (CSF). These were eluted from Lipidex-1000 and analyzed by SDS-NuPAGE followed by Western blotting. Using this methodology, we have been able to extract full-length and truncated forms of alpha-syn from brain lysates. We also extracted low levels of beta-syn from DLB brains, but failed to extract any gamma-syn. We were able to capture only full-length monomeric alpha-syn from normal human CSF. Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic.
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PMID:An investigation into the lipid-binding properties of alpha-, beta- and gamma-synucleins in human brain and cerebrospinal fluid. 1769 32