The treatment of tubulin with subtilisin resulted in a significant decrease the ability to assemble. addition taxol reduced effect on assembly digested protein. Limited proteolysis by affected simultaneously both alpha- and beta-subunits, it appearance two major cleavage fragments (32 20 kilodaltons) or an alternative pattern yielding (48 4 kilodaltons). smallest peptide (4 also 20-kilodalton fragment are localized C-terminal region alpha-subunit. Digested can assemble into sheet-shaped...

Limited proteolysis of phosphocellulose-purified tubulin with subtilisin resulted in cleavage both alpha and beta subunits, the formation two major fragments (S alpha, S beta, 48 kDa) a small peptide (4 containing carboxyl-terminal region tubulin. Interestingly, cleaved under present conditions showed an increased ability to assemble into large polymers absence MAPs that do not promote assembly undigested tubulin--i.e., low magnesium concentrations taxol polyalcohols. The critical for...

Hyperinsulinemia as well type II diabetes mellitus are among the risk factors for Alzheimer's disease (AD). However, molecular and cellular basis that link insulin resistance disorders with AD far from clear. Here, we discuss potential mechanisms may explain participation of these metabolic in pathogenesis AD. The human brain uses glucose a primary fuel; secreted by pancreas cross blood-brain barrier (BBB), reaching neurons glial cells, exerts region-specific effect on metabolism. Glucose...

The key target of this study was the tau protein kinase II system (TPK II) involving catalytic subunit cdk5 and regulatory component p35. TPK is one phosphorylating systems in neuronal cells, thus regulating its functions cytoskeletal dynamics extension processes. This research led to demonstration that treatment rat hippocampal cells culture with fibrillary β‐amyloid (Aβ) results a significant increase enzymatic activity. Interestingly, data also showed neurotoxic effect 1–20 μM Aβ on...

Cultures of cerebellar macroneurons were used to study the pattern expression, subcellular localization, and function neuronal cdk5 activator p35 during laminin-enhanced axonal growth. The results obtained indicate that laminin, an extracellular matrix molecule capable selectively stimulating extension promoting MAP1B phosphorylation at a proline-directed protein kinase epitope, stimulates increases its association with subcortical cytoskeleton, accelerates redistribution growth cones....

Neuroinflammation is a process related to the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Increasing sets evidence support major role deregulation interaction patterns between glial cells and neurons in pathway toward neuronal degeneration, we are calling neuroimmunomodulation AD. On basis hypothesis that pathological tau aggregates induce microglial activation with subsequent events neuroinflammatory cascade, have studied effects oligomeric species...

We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates tau protein (neurofibrillary tangles). Interestingly, these compounds, important medical applications in treatment allergies gastrointestinal disorders respectively, specifically bind to aggregated variants paired helical filaments isolated from brains Alzheimer's disease (AD) patients. These ligands appear be a powerful tool tag brain-isolated tau-aggregates...

The microtubule-associated tau protein participates in the organization and integrity of neuronal cytoskeleton. A nuclear form has been described non-neuronal cells, which displays a nucleolar localization during interphase but is associated with nucleolar-organizing regions mitotic cells. In present study, based on immunofluorescence, immuno-FISH confocal microscopy, we show that mainly at internal periphery nucleoli, partially colocalizing nucleolin human AT-rich α-satellite DNA sequences...

A set of different protein kinases have been involved in tau phosphorylations, including glycogen synthase kinase 3β (GSK3β), MARK kinase, MAP the cyclin‐dependent 5 (Cdk5) system and others. The latter include catalytic component Cdk5 regulatory proteins p35, p25 p39. its neuron‐specific activator p35 are essential molecules for neuronal migration laminar configuration cerebral cortex. Recent evidence that Cdk5/p35 complex concentrates at leading edge axonal growth cones, together with...

A number of psychiatric and neurodegenerative disorders, such as Alzheimer's disease, are characterized by abnormalities in the neuronal cytoskeleton. Here, we find that enhancement actin polymerization induced fibrillar amyloid-beta peptide (Abeta) is associated with increased activity Rac1/Cdc42 Rho GTPases. Rac1 upregulation involves participation Tiam1, a Rac guanine-nucleotide exchange factor, where Abeta exposure leads to Tiam1 activation Ca(2+)-dependent mechanism. These results point...

Platelets are a major peripheral reservoir of the amyloid-β protein precursor, so they have been considered as potential biological marker Alzheimer's disease (AD). Here, it is demonstrated that tau also present in platelets and