# Presentation: 905839

## The Programmed Cell

**The Programmed Cell**
**Death Pathway of Trypanosomatid **
**Parasites **

- Alain Debrabant, Ph.D.

**Laboratory of Bacterial Parasitic and Unconventional Agents**
**Division of Emerging and Transfusion Transmitted Diseases**
**OBRR/CBER / FDA**

## Slide 2

## Programmed Cell Death (PCD) 

**Death signals**

**Cell death**

**Programmed Cell Death (PCD) **

- N

**(apoptosis)**

**Caspases**

**Nucleases** (CAD, EndoG)

## Objectives

**Objectives**

**Identify the effector molecules of the *****Leishmania***** **
**programmed cell death pathway**

**Effector molecules of trypanosomatid PCD pathways **
**are potential **_**new targets**_** for drugs that would selectively **
**trigger parasite death**

_**Outcomes**_

**Better understanding of parasite growth **
**and pathogenesis**

## Cell death

**. Growth arrest**
**. Anti-leishmanial drugs**
**. Oxidative stress (H****2****O****2****)**

**. Anexin V positive**
**. PI positive**

**. Change in mitochondrial**
**    ****membrane potential**
**. Cytochrome C release**

**N**

**. TUNEL positive**
**. DNA ladder **

**2**

**4**

**?**

**1**

**?**

**3**

**Cell death**

**K**

**Death Signals**

**Mitochondria**
**(kinetoplast)**

**Plasma membrane**

**Activation of protease(s)**

**“****Caspase-like” activities**

**Nucleus**

- 1-5: possible sequence of events
- N: nucleus; K: kinetoplast

**5**

**Programmed Cell Death Pathway in *****Leishmania***** **

**Notes:**

Update slide including results from other groups

## Leishmania donovani metacaspases

***Leishmania donovani***** metacaspases**

## Cell death

**. Growth arrest**
**. Anti-leishmanial drugs**
**. Camptothecin**
**. H2O2**

**. Anexin V positive**
**. PI positive**

**. Change in mitochondrial**
**    ****membrane potential**
**. Cytochrome C release**

**N**

**. TUNEL positive**
**. DNA ladder **

**2**

**4**

**?**

**1**

**?**

**3**

**Cell death**

**K**

**Death Signals**

**Mitochondria**
**(kinetoplast)**

**Plasma membrane**

**Activation of protease(s)**

**“****Caspase-like” activity**
**Metacaspase activity**

**Nucleus**

- 1-5: possible sequence of events
- N: nucleus; K: kinetoplast

**5**

**Programmed Cell Death Pathway in *****Leishmania***** **

**Notes:**

Update slide including results from other groups

## Leishmania Endonuclease G

***Leishmania *****Endonuclease***** *****G**

## Summary

**Summary**

_**Results**_**:**** **
**We identified and characterized two effector molecules **
**of the *****Leishmania***** PCD pathway **
**(metacaspases and endonuclease-G)**

_**Goal**_**:**
**Identify effectors molecules of *****Leishmania *****PCD pathway**

_**Outcomes**_**:**** **
**1. Better understanding of *****Leishmania***** growth and pathogenesis**
**2. Effector molecules of PCD represent new drug targets**

## Acknowledgments

_**DETTD / CBER**_

_**NIH / Laboratory of Parasitic Diseases**_

**Nancy Lee ****(Metacaspase)**
**S. Gannavaram ****(EndoG)**
**A. Selvapandiyan**
**Robert Duncan**
**Hira Nakhasi**

**Sylvie Bertholet**
**Shaden Kamhawi**

**Acknowledgments**

_**University of Illinois**_

**Roberto Docampo**

_**Summer Students**_
**Chetan Vedvyas**
**Vaibhav Bist**

## Thank You 

**Thank You **