INVESTIGADORES
PEREIRA Claudio Alejandro
artículos
Título:
Amino acid metabolic routes in Trypanosoma cruzi: possible therapeutic targets against Chagas'disease.
Autor/es:
SILBER, ARIEL; WALTER COLI,; HENNING ULRICH,; MANSO ALVES, MARIA; PEREIRA, CA
Revista:
Current Drug Targets Infectious Disorders
Editorial:
Bentham Science Publishers Ltd.
Referencias:
Año: 2005 vol. 5 p. 53 - 64
ISSN:
1568-0053
Resumen:
Chagas´ disease is a zoonosis caused by the parasite Trypanosoma cruzi, a haematic protozoan, transmitted by
insects from the Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
insects from the Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
Trypanosoma cruzi, a haematic protozoan, transmitted by
insects from the Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with
11 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two
drugs, nifurtimox® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
® and benznidazole®, that were discovered more than thirty years ago, and are mainly successful during
the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy
is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on
patients.
Trypanosoma cruzi has a metabolism largely based on the consumption of amino acids, mainly proline, aspartate and
glutamate, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle. These amino
acids also participate in the differentiation process of the replicative non-infective form (epimastigote) to the nonreplicative
infective form (trypomastigote). In particular, the participation of proline in the intracellular differentiation
cycle, which occurs in the mammalian host, was recently demonstrated. In addition, an arginine kinase has been described
in T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
glutamate, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle. These amino
acids also participate in the differentiation process of the replicative non-infective form (epimastigote) to the nonreplicative
infective form (trypomastigote). In particular, the participation of proline in the intracellular differentiation
cycle, which occurs in the mammalian host, was recently demonstrated. In addition, an arginine kinase has been described
in T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
has a metabolism largely based on the consumption of amino acids, mainly proline, aspartate and
glutamate, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle. These amino
acids also participate in the differentiation process of the replicative non-infective form (epimastigote) to the nonreplicative
infective form (trypomastigote). In particular, the participation of proline in the intracellular differentiation
cycle, which occurs in the mammalian host, was recently demonstrated. In addition, an arginine kinase has been described
in T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.
T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy
reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken
together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic
drugs.