Brain nucleoside recycling

Ipata, Piero Luigi; Balestri, Francesco; Tozzi, Maria Grazia; Camici, Marcella

doi:10.1007/s11306-012-0457-x

Cited by 6 publications

(12 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metabolism of nucleosides is well understood in the brain [30,41,[71][72][73][74][75][76][77]. Purines and pyrimidines are synthesized (de novo) from precursor molecules such as carbon dioxide, aspartate, 5-phosphoribosyl-1-pyrophosphate (PRPP), glutamine, glycine and formyl groups, as well as from aspartate and carbamyl-phosphate.…”

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

“…The catabolism of nucleotides may occur through several different routes in the brain [30,40,41,72]. Adenosine triphosphate (ATP), Urd triphosphate (UTP) and Guo triphosphate (GTP) are degraded to their corresponding monophosphates, namely, Ado monophosphate (AMP), Urd monophosphate (UMP) and Guo monophosphate (GMP), respectively, by nucleoside di-and triphosphate phosphatases ( Fig.…”

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

“…The extracellular (EC) level of Ado is maintained and regulated by ecto-5'-nucleotidase (ecto-5'NT, eN, e5'NT), ecto-Ado kinase (ecto-ADK) and ectoAdo deaminase (ecto-ADA) [72,75,76] (Fig. 1).…”

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

“…Because IL-1 and LPS increased ADK expression in astrocyte cultures [156], the link between the LPS-induced increase in IL-1 and absence epileptic activity [192,193] may be the decreased level of endogenous anticonvulsant Ado by ADK. In addition, LPS and IL-1 induced the release of ATP from hippocampal slices [194], which may be metabolized extracellularly to Ado by ectonucleotidases [72,75,76] resulting in stimulation of A 2A receptors, which may downregulate the expression of A 1 receptors [195] and enhance Ado uptake by ENT transporters [196]. All of these effects may increase epileptic activity by decreased Ado-induced inhibition via A 1 receptors.…”

Section: The Specific Role Of Adenosine In Inflammationinduced Epilepsymentioning

confidence: 99%

“…Intrahippocampal transplantation of Ado-releasing cells suppressed seizures in a kainic acid mouse model [165]. In addition, Ado accumulation, which may result in side effects, is precluded by EC metabolism of Ado by ecto-ADA [72,75,76]. Despite these results, implantation of Ado-releasing cells has advantages (e.g., there is no need to refill the system as with pumps and polymers) and disadvantages (e.g., the lack of control of drug release and the unknown longterm effects) [404].…”

Section: New Developmentsmentioning

confidence: 99%

See 4 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

View full text Add to dashboard Cite

Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

show abstract

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

Section: The Specific Role Of Adenosine In Inflammationinduced Epilepsymentioning

confidence: 99%

Section: New Developmentsmentioning

confidence: 99%

See 3 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

View full text Add to dashboard Cite

show abstract

Nucleoside recycling in the brain and the nucleosidome: a complex metabolic and molecular cross-talk between the extracellular nucleotide cascade system and the intracellular nucleoside salvage

Ipata

Pesi

2015

Metabolomics

View full text Add to dashboard Cite

The transports of nucleosides from blood into\ud neurons and astrocytes are essential prerequisites to enter\ud their metabolic utilization in brain. Adult brain does not\ud possess the de novo nucleotide synthesis, and maintains its\ud nucleotide pools by salvaging preformed nucleosides\ud imported from liver. Once nucleosides enter the brain\ud through the blood brain barrier and the nucleoside transporters,\ud they become obligatory precursors for the synthesis\ud of RNA and DNA and a plethora of other important\ud functions. However, an aliquot of nucleotides are transferred\ud into vesicular nucleotide transporters, and then in the\ud extracellular space by exocytosis of the vesicles, where\ud ATP and UTP interact with a vast heterogeneity of purine\ud and pyrimidine receptors. Their signal actions are terminated\ud by the ectonucleotidase cascade system, which\ud degrades ATP and UTP into adenosine and uridine,\ud respectively. The low specificity of the vesicular nucleotide\ud transporters may explain the presence in the extracellular\ud space of GTP and CTP, which are equally degraded to their\ud respective nucleosides by the ectonucleotidases. The main\ud four nucleosides are re-imported either into the same cell,\ud or in adjacent cells, e.g. between two astrocytes, or\ud between a neuron and an astrocyte, to regenerate nucleoside\ud triphosphates. The molecular network of this metabolic\ud cross-talk, involving the ectonucleotidases, the\ud nucleoside transporters, the nucleotide salvage system, the\ud nucleotide transport into the vesicular nucleotide transporters,\ud and the exocytotic release of nucleotides, called by\ud us the ‘‘nucleosidome’’, serves the nucleoside recycling in\ud the brain, with a considerable spatial–temporal advantage

show abstract

The furanosidic scaffold of d-ribose: a milestone for cell life

Corso

Cappiello

Moschini

et al. 2019

Biochemical Society Transactions

View full text Add to dashboard Cite

The recruitment of the furanosidic scaffold of ribose as the crucial step for nucleotides and then for nucleic acids synthesis is presented. Based on the view that the selection of molecules to be used for relevant metabolic purposes must favor structurally well-defined molecules, the inadequacy of ribose as a preferential precursor for nucleotides synthesis is discussed. The low reliability of ribose in its furanosidic hemiacetal form must have played ab initio against the choice of d-ribose for the generation of d-ribose-5-phosphate, the fundamental precursor of the ribose moiety of nucleotides. The latter, which is instead generated through the ‘pentose phosphate pathway’ is strictly linked to the affordable and reliable pyranosidic structure of d-glucose.

show abstract

Brain nucleoside recycling

Cited by 6 publications

References 71 publications

The Antiepileptic Potential of Nucleosides

The Antiepileptic Potential of Nucleosides

Nucleoside recycling in the brain and the nucleosidome: a complex metabolic and molecular cross-talk between the extracellular nucleotide cascade system and the intracellular nucleoside salvage

The furanosidic scaffold of d-ribose: a milestone for cell life

Contact Info

Product

Resources

About