Neurite

Within the nervous system, ChEs were shown to be involved in membrane conductance and transmission of excitatory amino acids, learning and memory, neurite growth, neuritic translocation and acute stress reactions. Recent findings propose AChE s involvement in apoptosome formation [2]. 

Furthermore, PKCe is required for nerve growth factor-induced activation of mitogen-activated protein kinases and neurite outgrowth by ethanol. It is also required for ethanol-induced increases in N-type voltage-gated calcium channels in PC 12 neural cells. 

LPA LPA Ubiquitous Gj/o. Gq, G12/13 Proliferation, survival, neurite retraction, brain development... 

GPR63 (LPA5) Stress fibre formation, neurite retraction... 

Neurodegeneration. Figure 3 Illustration of synaptic (neuritic) apoptosis. A pyramidal neuron is depicted with cortical afferents synapsing on its dendrites. Localized apoptotic mechanisms lead to the release of cytochrome c from the mitochondria and an increase in the concentration of activated caspase-3 in a presynaptic terminal that is synapsing on a dendritic spine. Increased caspase-3 activity results in a localized breakdown of this nerve terminal and its synapse. Subsequently, the postsynaptic dendritic spine retracts and disappears (Figure modified from Glantz et al. [5] [3]). 

Poly-L-lysine-blended chitosan, collagen-blended chitosan and albumin-blended chitosan were also considered, with collagen control material. Culture of PC12 cells and fetal mouse cerebral cortex cells on these biomaterials was used to evaluate their nerve cell affinity. The composite materials, had significantly improved nerve cell affinity compared to chitosan. Poly-L-lysine-blended chitosan exhibited the best nerve cell affinity and was a better material in promoting neurite outgrowth than collagen [328]. 

Cell migration and cytoplasmic movement involve predominantly actin filaments in the locomotion of neutrophilic granulocytes, both actin filaments and microtubules in the elongation of neuronal growth cones and migration of neurites, and both actin and myosin in cytokinesis and the contraction of skeletal and cardiac muscle. 

Rauvala, H., Pihlaskari, R., Laitinin, J., Merenmies, J. (1989). Extracellular adhesive molecules in neurite growth. Biosci. Rep. 9, 1—12. 

Emetine emetine is still used at high doses for the treatment of patients with severe amebiasis. Muscle damage is uncommon but when it does occur can be a severe generalized necrotizing myopathy. The outcome is, at times, fatal, especially when an emetine-induced cardiomyopathy is also present. Despite the suggestion that there may be neuritic changes, there is no evidence that emetine damages peripheral nerve. The myopathy is usually painful but reversible. The mechanism of action of emetine is unknown. 

Figure 4. Neurite outgrowth by LA-N-1 human neuroblastoma cells in culture. LA-N-1 human PNS neuroblastoma cells were grown for five days in N2 medium (as described by Bottenstein and Sato, 1979) on a polylysine and fibronectin-modified surface. The cells were plated in clumps, rather than as a single cell suspension, which enhances neurite extension. Very long processes result, and exhibit varicosities along their length. Most of the cells have migrated from the central clump. (Photo courtesy of Dr. jane Bottenstein.)...

Holmes TC, de Lacalle S, Su X et al (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci 97 6728-6733... 

There is an association between patients possessing the apo E4 aiieie and the incidence of Aizheimer s disease. Apparentiy, apo E4 binds more avidiy to 3-amyioid found in neuritic piaques. 

Cui L, Locatelli L et al (1997) Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells. J Pharmacol Exp Ther 280(3) 1228-1234 Dal Pan GJ, Glass JD et al (1994) Clinicopathologic correlations of HIV-l-associated vacuolar myelopathy an autopsy-based case-control study. Neurology 44(11) 2159-2164 Dalakas MC (2001) Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst 6(l) 14-20 Dalakas MC, Semino-Mora C et al (2001) Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2 3 -dideoxycytidine (ddC). Lab Invest 81(11) 1537-1544... 

Xia M, Qin S, McNamara M, Mackay C, Hyman BT (1997) lnterleukin-8 receptor B immunore-activity in brain and neuritic plaques of Alzheimer s disease. Am J Pathol 150 1267-1274 Xia MQ, Bacskai BJ, Knowles RB, Qin SX, Hyman BT (2000) Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes in vitro ERKl/2 activation and role in Alzheimer s disease. J Neuroimmunol 108 227-235 Xia MQ, Qin SX, Wu LJ, Mackay CR, Hyman BT (1998) Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their Ugands in normal and Alzheimer s disease brains. Am J Pathol 153 31-37... 

Figure 2.4 Noradrenergic inhibition of Ca " currents and transmitter release in sympathetic neurons and their processes, (a) Inhibition of currents through N-type Ca " channels by external application of noradrenaline (NA) or by over-expression of G-protein P y2 subunits, recorded from the soma and dendrite of a dissociated rat superior cervical sympathetic neuron. Currents were evoked by two successive 10 ms steps from —70 mV to OmV, separated by a prepulse to -1-90 mV. Note that the transient inhibition produced by NA (mediated by the G-protein Go) and the tonic inhibition produced by the G-protein Piy2 subunits were temporarily reversed by the -1-90 mV depolarisation. (Adapted from Fig. 4 in Delmas, P et al. (2000) Nat. Neurosci. 3 670-678. Reproduced with permission), (b) Inhibition of noradrenaline release from neurites of rat superior cervical sympathetic neurons by the 2-adrenoceptor stimulant UK-14,304, recorded amperometrically. Note that pretreatment with Pertussis toxin (PTX), which prevents coupling of the adrenoceptor to Gq, abolished inhibition. (Adapted from Fig. 3 in Koh, D-S and Hille, B (1997) Proc. Natl. Acad. Sci. USA 1506-1511. Reproduced with permission)...

Figure 18.1 Typical tangle (T) and plaque (P) as visualised by silver impregnation in the cerebral cortex of a case of Alzheimer s disease. The extracellular plaque (10-50 pm diameter) consists of a central core of amyloid surrounded by glial processes and a number of neurites in a ring formation. The intracellular cytoplasmic tangle is composed of helical filaments in a paired format. (Reproduced with permission of Academic Press from Wischik and Crowther 1986)...

If immune reactions are to be avoided then recombinant human factor should be used and that cannot be produced in large quantities. In any case, it is a large protein that will have to be injected directly into the brain. Even if these problems can be overcome the spread and intensity of any NGF effect has to be restricted so that excessive neuritic growth and inappropriate increases in synaptic connections do not occur. 

Landsberg, J.P., McDonald, B. and Watt, F. (1992). Absence of aluminium in neuritic plaque cores in Alzheimer s disease. Nature 360, 65-68. 

Rees, S. and Cragg, B. (1983). Is silica involved in neuritic (senile) plaque formation Acta Neuropath. 59, 31-40. 

Kitt, C.A. Walker, L.C. Molliver. M.E. and Price, D.L. Serotoninergic neurites in senile plaques in cingulate cortex of aged nonhuman primate. Synapse 3 12-18, 1989. 

An assay that produces multiple biological readouts. Most commonly used in relation to the mathematical analysis of an image acquired using an automated microscope whereby analysis algorithms quantify cellular parameters (e.g., number, motility, neurite outgrowth, size, shape) and subcellular events (e.g., receptor internalization, protein translocation, protein expression nuclei shape). 

Pathologic hallmarks of the disease in the brain include neurofibrillary tangles and neuritic plaques (senile plaques)... 

The pathologic hallmarks of the disease in the brain include neurofibrillary tangles and neuritic plaques made up of various proteins, which result in a shortage of the neurotransmitter acetylcholine. These are primarily located in brain regions involved in learning, memory, and emotional behaviors such as the cerebral cortex, hippocampus, basal forebrain, and amygdala.11... 

Neuritic or senile plaques are extracellular protein deposits of fibrils and amorphous aggregates of P-amyloid protein.11 This formed protein is central to the pathogenesis of AD. The P-amyloid protein is present in a non-toxic, soluble form in human brains. In AD, conformational changes occur that render it insoluble and cause it to deposit into amorphous diffuse plaques associated with dystrophic neuritis.14 Over time, these deposits become compacted into plaques and the P-amyloid protein becomes fibrillar and neurotoxic. Inflammation occurs secondary to clusters of astrocytes and microglia surrounding these plaques. 

Neuritic (senile) plaques Microscopic lesions composed of fragmented axon terminals and dendrites surrounding a core of amyloid seen in the cerebral cortex in Alzheimer s disease. 

Diffuse Lewy body Cerebrocortical regions, a-Synuclein Lewy bodies and neurites... 

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