<unk>  in solution is considered to be an intrinsically disordered protein, i.e. it lacks a single stable 3D structure. As of 2014, an increasing number of reports suggest, however, the presence of partial structures or mostly structured oligomeric states in the solution structure of<unk>  even in the absence of lipids. This trend is also supported by a large number of single molecule (optical tweezers) measurements on single copies of monomeric<unk>  as well as covalently enforced dimers or tetramers of<unk> .<unk>  is specifically upregulated in a discrete population of presynaptic terminals of the brain during a period of acquisition-related<unk> aptic rearrangement. It has been shown that<unk>  significantly interacts with tubulin, and that<unk>  may have activity as a potential microtubule-associated protein, like tau. Evidence suggests that<unk>  functions as a molecular chaperone in the formation of SNARE complexes. In particular, it simultaneously binds to phospholipids of the plasma membrane via its N-terminus domain and to<unk> aptobrevin-2 via its C-terminus domain, with increased importance during<unk> aptic activity. Indeed, there is growing evidence that<unk>  is involved in the functioning of the neuronal Golgi apparatus and vesicle trafficking. Apparently,<unk>  is essential for normal development of the cognitive functions. Knock-out mice with the targeted inactivation of the expression of<unk>  show impaired spatial learning and working memory. Interaction with lipid membranes Experimental evidence has been collected on the interaction of<unk>  with membrane and its involvement with membrane composition and turnover. Yeast genome screening has found that several genes that deal with lipid metabolism and mitochondrial fusion play a role in<unk>  toxicity. Conversely,<unk>  expression levels can affect the viscosity and the relative amount of fatty acids in the lipid bilayer.<unk>  is known to directly bind to lipid membranes, associating with the negatively charged surfaces of phospholipids.<unk>  forms an extended helical structure on small unilamellar vesicles. A preferential binding to small vesicles has been found. The binding of<unk>  to lipid membranes has complex effects on the latter, altering the bilayer structure and leading to the formation of small vesicles.<unk>  has been shown to bend membranes of negatively charged phospholipid vesicles and form tubules from large lipid vesicles. Using cryo-EM it was shown that these are micellar tubes of ~5-6 nm diameter.<unk>  has also been shown to form lipid disc-like particles similar to apolipoproteins. EPR studies have shown that the structure of<unk>  is dependent on the binding surface. The protein adopts a broken-helical conformation on lipoprotein particles while it forms an extended helical structure on lipid vesicles and membrane tubes. Studies have also suggested a possible antioxidant activity of<unk>  in the membrane. Photomicrographs of regions of substantia nigra in a patient showing Lewy bodies and Lewy neurites in various magnifications Membrane interaction of<unk>  modulates or affects its rate of aggregation. The membrane-mediated modulation of aggregation is very similar to that observed for other amyloid proteins such as IAPP and abeta. Aggregated states of<unk>  permeate the membrane of lipid vesicles. They are formed upon interaction with peroxidation-prone polyunsaturated fatty acids (PUFA) but not with monounsaturated fatty acids and the binding of lipid autoxidation-promoting transition metals such as iron or copper provokes oligomerization of<unk> . The aggregated<unk>  has a specific activity for peroxidized lipids and induces lipid autoxidation in PUFA-rich membranes of both neurons and astrocytes, decreasing resistance to apoptosis. Lipid autoxidation is inhibited if the cells are pre-incubated with isotope-reinforced PUFAs (D-PUFA).
Alpha-synuclein
Kamino bodies
Lewy body
Neurofibrillary tangle
Amyloid beta
Neurofilament light polypeptide
Hirano body
Wild-type transthyretin amyloid