Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In neurons, neuropeptides and other synaptic components are transported down the axon to the synapse in vesicles using molecular motors of the kinesin family. In the synapse, these neuropeptides are found in dense core vesicles (DCVs), and, following calcium-mediated exocytosis, they interact with receptors on the target cell. We have developed a rapid, large-scale technique for purifying peptide-containing DCVs from specific nuclei in the central nervous system. By using differential velocity gradient and equilibrium gradient centrifugation, neuropeptide-containing DCVs can be separated by size and density from optic nerve (ON) and its termini, the lateral geniculate nuclei and the superior colliculi. Isolated DCVs contain neuropeptides (substance P and brain-derived neurotrophic factor), synaptic vesicle (SV) membrane proteins (SV2, synaptotagmins, synaptophysin, Rab3 and synaptobrevin), SV-associated proteins (alpha-synuclein), secretory markers for DCVs previously isolated (secretogranin II), and beta-amyloid precursor protein. By using electron microscopic techniques, DCV were also visualized and shown to be immunoreactive for neuropeptides, neurotrophins, and SV membrane proteins. Because of the interesting group of physiological and potentially pathophysiological proteins associated with these vesicles; this isolation procedure, applicable to other CNS nuclei, should represent an important research tool.
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PMID:Isolation and characterization of substance P-containing dense core vesicles from rabbit optic nerve and termini. 1110 68

Tau and alpha-synuclein are both proteins implicated in the pathology of neurodegenerative disease. Here we have investigated the mechanisms of axonal transport of tau and alpha-synuclein, because failure of axonal transport has been implicated in the development of several neurodegenerative disorders. We found that the transport of both of these proteins depend on an intact microtubule- but not actin-cytoskeleton, and that tau and alpha-synuclein both move at overall slow rates of transport. We used time-lapse video microscopy to obtain images of live neurons that had been transfected with plasmids expressing proteins tagged with enhanced green fluorescent protein. We found that particulate structures containing tau or alpha-synuclein travel rapidly when moving along axons but spend the majority of the time paused, and these structures have similar characteristics to those previously observed for neurofilaments. The motile particles containing tau or alpha-synuclein colocalise with the fast-transporting molecular motor kinesin-1 in neurons. Co-immunoprecipitation experiments demonstrate that tau and alpha-synuclein are each associated with complexes containing kinesin-1, whereas only alpha-synuclein appears to interact with dynein-containing complexes. In vitro glutathione S-transferase-binding assays using rat brain homogenate or recombinant protein as bait reveals a direct interaction of kinesin-1 light chains 1 and 2 with tau, but not with alpha-synuclein. Our findings suggest that the axonal transport of tau occurs via a mechanism utilising fast transport motors, including the kinesin family of proteins, and that alpha-synuclein transport in neurons may involve both kinesin and dynein motor proteins.
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PMID:Molecular motors implicated in the axonal transport of tau and alpha-synuclein. 1617 37

There is increasing evidence that tau protein behaves in a prion-like manner in tauopathy. The stabilization of tau protein using a small molecular compound can limit tauopathy associated morbidity that advances with ageing. Here, a lab-on-a-chip experiment is reported, where gold citrate nanoparticles (5 nm, AuNPs) can remodel mutant tau protein (P301L) and prion, thus resolving the mutant tau- and prion-mediated impairment of kinesin cargo transport on microtubules. It is found that tau protein is overexpressed in Alzheimer's disease (AD) patient serum samples and the tau conformational change can also be affected in human serum samples of AD when treated with AuNPs ex vivo. Similarly, AuNPs reorganizing the prion protein and inducing conformational changes of prions in AD serum have been observed, while having no effect on alpha-synuclein in Parkinson patient serum. The mapping of AD serum mediated traffic jams, using particle tracking and mean square displacement analysis, and the observed recovery of uninterrupted processive motor functions by AuNP treatment show that kinesin cargo assays might be a useful method for future ex vivo validation of a targeted therapy against tauopathy before administration, a viable option to combat various neurodegenerative disorders arising from the susceptibility of amyloidogenic proteins toward aggregation.
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PMID:Remodeling Tau and Prion Proteins Using Nanochaperons. 3264 92