\ ALS Research \ Tanguay Lab Continues Innovative Research
Tanguay was recently awarded a one-year, $40,000 grant for his project “Over expression of small mitochondrial chaperones in a mouse model of ALS”. The award is jointly funded by the ALS Society of Canada and The ALS Association.
Tanguay and his colleagues, in collaboration with Jean-Pierre Julien, PhD, will produce mice that make more than the usual amount of heat shock proteins (hsp), naturally-occurring intra-cellular protectors. The mice will also produce the mutated form of the SOD1 protein, which is linked to some inherited forms of ALS.
The targeted hsps are active in the mitochondria, which generate energy for cellular function. If results indicate that high levels of the mitochondrial hsp help in the SOD1 mouse model, this could lead to a therapeutic treatment for ALS.
Hsps are conserved proteins induced by potentially damaging stresses. They are responsible for ensuring that proteins fold and are trafficked properly in cells. The Tanguay lab has been working on the functions of hsps for several years using Drosophila (fruit flies). They have focused on heat shock protein 22 (hsp22), which is upregulated during the aging process. Over-expressing hsp22 in the motor neurons of Drosophila has been shown to boost resistance to various stresses, increase longevity and benefit locomotor activity.
“Based on the preliminary results, we think that over expression of small heat shock proteins (shsp), especially mitochondrial ones, could be beneficial in preventing or delaying the onset of ALS,” says Tanguay.
The Tanguay lab has conducted structure and function experiments to determine if the chaperone function and/or the location of hsp22 in the mitochondria contribute to longevity. They are working to identify hsp22 partners to see if they play a role in longevity as well. The Tanguay lab also investigates the regulation of hsp22 as it is transcribed from DNA to RNA and the relation of hsp22 to the insulin/insulin-like growth factor signalling pathway.
The lab’s interest in hsps extends to a collaborative project that emphasizes environmental health. With the School of Public Health of Tongji Medical College in Wuhan, China, the Tanguay lab is conducting a project on the genetic variations in hsp70 genes and antibodies to hsps in coronary heart diseases.
Finally, the Tanguay lab is studying a human hereditary disease, tyrosinemia, which has a high incidence among French-Canadians. Incidence of the disease is particularly high in northeastern Quebec, where one in 22 people is a carrier. Tyrosinemia is a recessive metabolic disorder affecting the liver and caused by a deficiency of the last enzyme in the degradation pathway of the amino acid tyrosine. The disease affects children and has high rates of both morbidity and mortality. The only effective therapy is liver transplantation, though a drug, Orfadin, has shown promising short-term results. The goal of the Tanguay lab is to understand the molecular and cellular basis of the pathologies associated with tyrosinemia. Using mouse models, the lab is working to explain the cause of liver cancer, a consistent feature of the disease, and understand the mechanisms underlying the mutation-causing and cell-destroying properties of the toxic metabolic byproducts of tyrosine. This knowledge is important for disease treatment and could be applicable to therapeutic liver repopulation.
The Tanguay lab is funded by the Canadian Institutes of Health Research, including the China-Canada Joint Health Research Initiative program and the European Commission in the Consortium Project MiMage.
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Tanguay Lab Continues Innovative Research
Robert Tanguay, PhD, of Université Laval, thinks excess can be a good thing.Tanguay was recently awarded a one-year, $40,000 grant for his project “Over expression of small mitochondrial chaperones in a mouse model of ALS”. The award is jointly funded by the ALS Society of Canada and The ALS Association.
Tanguay and his colleagues, in collaboration with Jean-Pierre Julien, PhD, will produce mice that make more than the usual amount of heat shock proteins (hsp), naturally-occurring intra-cellular protectors. The mice will also produce the mutated form of the SOD1 protein, which is linked to some inherited forms of ALS.
The targeted hsps are active in the mitochondria, which generate energy for cellular function. If results indicate that high levels of the mitochondrial hsp help in the SOD1 mouse model, this could lead to a therapeutic treatment for ALS.
Hsps are conserved proteins induced by potentially damaging stresses. They are responsible for ensuring that proteins fold and are trafficked properly in cells. The Tanguay lab has been working on the functions of hsps for several years using Drosophila (fruit flies). They have focused on heat shock protein 22 (hsp22), which is upregulated during the aging process. Over-expressing hsp22 in the motor neurons of Drosophila has been shown to boost resistance to various stresses, increase longevity and benefit locomotor activity.
“Based on the preliminary results, we think that over expression of small heat shock proteins (shsp), especially mitochondrial ones, could be beneficial in preventing or delaying the onset of ALS,” says Tanguay.
The Tanguay lab has conducted structure and function experiments to determine if the chaperone function and/or the location of hsp22 in the mitochondria contribute to longevity. They are working to identify hsp22 partners to see if they play a role in longevity as well. The Tanguay lab also investigates the regulation of hsp22 as it is transcribed from DNA to RNA and the relation of hsp22 to the insulin/insulin-like growth factor signalling pathway.
The lab’s interest in hsps extends to a collaborative project that emphasizes environmental health. With the School of Public Health of Tongji Medical College in Wuhan, China, the Tanguay lab is conducting a project on the genetic variations in hsp70 genes and antibodies to hsps in coronary heart diseases.
Finally, the Tanguay lab is studying a human hereditary disease, tyrosinemia, which has a high incidence among French-Canadians. Incidence of the disease is particularly high in northeastern Quebec, where one in 22 people is a carrier. Tyrosinemia is a recessive metabolic disorder affecting the liver and caused by a deficiency of the last enzyme in the degradation pathway of the amino acid tyrosine. The disease affects children and has high rates of both morbidity and mortality. The only effective therapy is liver transplantation, though a drug, Orfadin, has shown promising short-term results. The goal of the Tanguay lab is to understand the molecular and cellular basis of the pathologies associated with tyrosinemia. Using mouse models, the lab is working to explain the cause of liver cancer, a consistent feature of the disease, and understand the mechanisms underlying the mutation-causing and cell-destroying properties of the toxic metabolic byproducts of tyrosine. This knowledge is important for disease treatment and could be applicable to therapeutic liver repopulation.
The Tanguay lab is funded by the Canadian Institutes of Health Research, including the China-Canada Joint Health Research Initiative program and the European Commission in the Consortium Project MiMage.
| Posted On: Thursday, January 03, 2008 Modified: Thursday, January 03, 2008 Category: ALS Research Posted By: |