Role of spermine in amyloid ?-peptide-associated free radical-induced neurotoxicity

Yatin, Servet; Yatin, Mustafa; Varadarajan, S.; Ain, Kenneth B.; Butterfield, D. Allan

doi:10.1002/1097-4547(20010301)63:5<395::aid-jnr1034>3.0.co;2-q

Cited by 82 publications

(52 citation statements)

References 54 publications

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“…Increased levels of three polyamines, putrescine, spermidine and spermine, have been reported in brain tissue and plasma from AD patients (Inoue et al, 2013;Trushina et al, 2013). The underlying explanation for this is that Aβ causes up-regulation of polyamine uptake and increased ornithine decarboxylase activity, which leads to increased polyamine synthesis (Yatin et al, 1999;Yatin et al, 2001). Polyamines, like spermidine and spermine are positive modulators of the N-Methyl-D-Aspartate (NMDA) receptor.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

Pan

Nasaruddin

Elliott

et al. 2016

Neurobiology of Aging

107

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The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon the metabolome is still not understood, nor is it known how disturbances change as the disease progresses. For the first time we have profiled longitudinally (6, 8, 10, 12 and 18 months) both the brain and plasma metabolome of APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT mice at 8, 10 and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched chain amino acids and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis was evident in two age groups. AD-like pathology therefore impacts greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

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Section: Discussionmentioning

confidence: 99%

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

Pan

Nasaruddin

Elliott

et al. 2016

Neurobiology of Aging

107

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“…Dopamine, Norepinephrine, and Serotonin Transporter Assays. The generation of stable human DAT-, NET-, and SERTtransfected HEK293 cells has been described previously Yatin et al, 2001;Verrico et al, 2005). Assays to measure drug inhibition of [ 3 H]monoamine transport were performed to determine IC 50 values, as described previously Verrico et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Modafinil Occupies Dopamine and Norepinephrine Transporters in Vivo and Modulates the Transporters and Trace Amine Activity in Vitro

Madras¹,

Xie²,

Lin³

et al. 2006

J Pharmacol Exp Ther

304

254

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“…The polyamine levels in the substantia nigra of diseased human brains of individuals exhibiting neurological disorders, including PD, are not lowered, suggesting that the regulation of the substances is well maintained even in degenerating cells (37). Spermine may serve to protect neuronal cells from oxidative stress (38), a condition known to induce aggregation of the amyloid A␤ peptide, the major component of amyloid deposits associated with Alzheimer's disease. It was also shown in cultured neuronal cells that the A␤ peptide combined with spermine is more toxic than the peptide alone (39).…”

mentioning

confidence: 99%

Cellular Polyamines Promote the Aggregation of α-Synuclein

Antony¹,

Hoyer²,

Cherny³

et al. 2003

Journal of Biological Chemistry

181

187

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The cellular polyamines putrescine, spermidine, and spermine accelerate the aggregation and fibrillization of ␣-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease. Circular dichroism and fluorometric thioflavin T kinetic studies showed a transition of ␣-synuclein from unaggregated to highly aggregated states, characterized by lag and transition phases. In the presence of polyamines, both the lag and transition times were significantly shorter. All three polyamines accelerated the aggregation and fibrillization of ␣-synuclein to a degree that increased with the total charge, length, and concentration of the polyamine. Electron and scanning force microscopy of the reaction products after the lag phase revealed the presence of aggregated particles (protofibrils) and small fibrils. At the end of the transition phase, ␣-synuclein formed long fibrils in all cases, although some morphological variations were apparent. In the presence of polyamines, fibrils formed large networks leading ultimately to condensed aggregates. In the absence of polyamines, fibrils were mostly isolated. We conclude that the polyamines at physiological concentrations can modulate the propensity of ␣-synuclein to form fibrils and may hence play a role in the formation of cytosolic ␣-synuclein aggregates.

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Role of spermine in amyloid ?-peptide-associated free radical-induced neurotoxicity

Cited by 82 publications

References 54 publications

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

Modafinil Occupies Dopamine and Norepinephrine Transporters in Vivo and Modulates the Transporters and Trace Amine Activity in Vitro

Cellular Polyamines Promote the Aggregation of α-Synuclein

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