protrombina, apo A-IV y Haptoglobina incrementadas en la enfermedad de huntington

1. “INCREASED PROTHROMBIN, APOLIPOPROTEIN A-IV, AND HAPTOGLOBIN IN THE CEREBROESPIAL FLUID OF PATIENTS WITH HUNTINGTON´S DISEASE.” Yen-Chu Huang. Maria Camila Montufar Pantoja Heyly Milena Ortega III SEMESTER 2011 UNIVERSIDAD PONTIFICIA BOLIVARIANA

2. GENERAL OBJETIVE Demonstrate how Prothrombin, Apolipoprotein A-IV and Haptoglobin concentrations in CSF has an important role in the HD evolution and compare these concentrations in HD and control patients .

3. INTRODUCTION HD is a hereditary, degenerative brain disorder. It is caused by an unstable CAG trinucleotide. Today there are others proteins involved in HD development and symptoms (Apolopoprotein A-IV, Haptoglobin , Prothrombin) and its important to clarify throughproteomicsstudies in CSF wich are theconcentrations (up ordown) and ifthislevels of biomarkers are correlated in HD.

4. PROTHROMBIN Plasma protein synthesized in the liver. Itplaysanimportantfunctionin coagulation processby reaction with the thromboplastin enzyme , with Ca ++ cation and V activate factor as coenzymes. In HD prothrombin proinflammatoryagent : DISEASE STATUS BIOMARKER Xa Ca++ Va Tromboplastina

5. APOLIPOPROTEIN AIV (APO AIV) glycoprotein synthesized by the human intestine and liver The formation of chylomicrons acts as a signal for the induction of Apo AIV synthesis alters the activity of the enzymes (LPL and LCAT) of lipoprotein metabolism and cholesterol efflux from extrahepatic tissues Is involved in the long-term regulation of both food intake and body weight

6. HAPTOGLOBIN protein produced by the liver haptoglobin binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system It prevents loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin

7. ENFERMEDAD DE HUNITNGTON - HD Progressive neurodegenerative disorder with autosomaldominant inheritance: - MovementDisorders.- Cognitiveimpairment.- Psychiatricdisorders.

12. Reducción y alquilación.

13. Corte de la proteína serina proteasa tripsina

15. WESTERN BLOT Busco proteínas especificas Uso ac Uso técnica SDS-PAGE Separación de proteínas por electroforesis en gel

16. ELISA Ensayo por inmunoabsorción ligado a enzimas Fosfatasa alcalina—peroxidasa de rabano Detección ag-ac 3 tipos: Ensayo tipo sandwich Ensayo competitivo Ensayo indirecto

17. RESULTADOS Representative Western blots of prothrombin (72 kD) and albumin (64 kD) in CSF and serum of HD patients and their correspondingcontrols.

18. RESULTADOS Representative Western blots of Apo A-IV (46 kD) and albumin (64 kD) in CSF and serum, respectively, of HD patients and theircorrespondingcontrols (C).

19. RESULTADOS Qalb, CSF haptoglobin, and serumhaptoglobinconcentration in HD patients.

20. DISCUSSION

21. CONCLUTIONS Theproteomicstudies in CFS in patients HD and control patients are veryimportanttodeterminateiftheincreaselevels of Haptoglobin, Apolipoprotein A-IV and Prothrombin are correlatedwith HD development. Itisimportanttorecognizethisproteinslikespecificsbiomarkers in HD; thatswhytheconcentrations of eachonewerequantified in CSF and serum; thusindirectlyevaluatethe BBB integrity.

22. CONCLUTIONS To be able to correlate the levels of these proteins with other mental diseases such as Alzheimer's, multiple sclerosis, among others; allow us to determine whether the activity of proteins mentioned in the study are a common phenomenon in a variety of neurodegenerative-tive disease or are specifically for HD. Becouseof the intact values of BBB and the increase levels of proteins, it suggest that they are produced in the CNS itself and that the relation within de concentrations of proteins in CSF has nothing to do with the concentration of these in serum.

23. MAPA CONCEPTUAL

24. MAPA CONCEPTUAL

25. BIBLIOGRAFIA MARTINEZ, L. Biología Molecular. ED UPB. Segunda edición. Medellín. 2011. HUANG Y-C, TSENG M-Y, et al. Increasedprothrombin, Apolipoprotein A-IV, and Haptoglobin in thecerebrospinal fluid of patientswithHuntington`sdisease. Enero 31, 2011