Inhaled corticosteroids (ICS) and long-acting bronchodilators (LABAs) are used in the treatment of asthma. Resonance assignments were made using standard methods [HNCO, HN(CO)CA, HNCA, HNCACB, To determine the relative arrangement of monomers within the oligomer, we introduced the spin label 1-oxy1-2,2,5,5-tetramethylpyrroline-3-methyl-methanethiosulfonate (MTSL) at residue 9 after mutating it from serine to cysteine. Furthermore, given the far lower propensity of the native tetramer to aggregate into fibrils (Recombinant human αSyn was obtained from Anaspec. Cells were lysed using a microtip sonicator (Fischer Sonic Dismembrator, Model 300). GM1 Ganglioside (Fidia Farmaceutici). In some embodiments, a ligand-neuropharmaceutical agent fusion protein, which has both ligand binding and neuropharmaceutical characteristics, can be produced as a contiguous protein by using genetic engineering techniques.

We find that our tetrameric α-synuclein binds readily to phosphatidylethanolamine (PE)-rich liposomes, as reported in the literature for conventionally prepared a-synuclein (To date, most α-synuclein research has focused on characterizing its aggregation properties and searching for the elusive toxic form(s); less is known concerning its native structure and function. The MALDI was calibrated each time using a high-molecular-weight protein calibration standard, Protein Calibration Standard 1 (Bruker Daltonics), using gas phase dimers of standard proteins to extend the mass range of calibration. In some embodiments, the present invention provides methods comprising steps of administering to a patient suffering from or susceptible to a synucleinopathy disease, disorder or condition a composition comprising an amount of an α-synuclein tetramer stabilizer sufficient to stabilize tetrameric α-synuclein.In some embodiments of the present invention, a synucleinopathy disease, disorder or condition is Parkinson's disease, dementia, or multiple system atrophy. The prophylactic administration of the agent serves to prevent or reduce the rate of onset of symptoms of Parkinson's disease (including idiopathic Parkinson's disease (PD)), Diffuse Lewy Body Disease (DLBD) also known as Dementia with Lewy Bodies (DLB), Combined Alzheimer's and Parkinson disease and multiple system atrophy (MSA).

Specifically, the present invention encompasses the recognition that prior efforts were directed at α-synuclein as an unstructured monomer rather than as a folded tetrameric structure.According to the present disclosure, α-synuclein acts as a tetramer; the present invention therefore provides systems, methods, and reagents that utilize and/or relate to tetrameric α-synuclein. Such embodiments provide information about ability of an agent to effectively resist denaturant effects over time, or in some cases correct the denaturing effect of the denaturant. The 1D strip was then equilibrated in 10 ml SDS sample buffer for 15 min, applied to a precast NuPAGE ZOOM 4-12% Bis-Tris gel (Invitrogen) and run for 200 V.Freshly collected erythrocytes were resuspended in 3-fold volume of ACK lysing buffer (Lonza, Walkersville USA), 45% (NH100 μl aliquots were either injected onto a Superdex 75 (10/300 GL) column or a Superose 12 (10/300 GL) (both from Amersham Biosciences) and eluted at a flow rate of 0.5 ml/min into 1 ml SEC fractions using 50 mM ammonium acetate, pH 8.5. Collectively, these α-synuclein associated disorders are referred to as synucleinophathies, and most are characterized by the presence of insoluble α-synuclein-rich aggregates called Lewy bodies (1-3).

Collectively, these α-synuclein associated disorders are referred to as synucleinophathies, and most are characterized by the presence of insoluble α-synuclein-rich aggregates called Lewy bodies (1-3).