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Related Concept Videos

Lysosomes01:31

Lysosomes

19.6K
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
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Core-Shell DNA-Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes.

Robert Knieß1, Wolf-Matthias Leeder1, Paul Reißig1

  • 1Molecular Genetics, Technical University Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany.

Chembiochem : a European Journal of Chemical Biology
|August 30, 2022
PubMed
Summary
This summary is machine-generated.

Researchers developed novel DNA-lipid nanoparticles to combat African trypanosomiasis. These nanoparticles effectively kill Trypanosoma brucei by disrupting parasite lysosomes, offering a promising new therapeutic strategy with reduced resistance risk.

Keywords:
African trypanosomesDNA nanoparticlesDNAzymeschemotherapeuticsdrug design

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Area of Science:

  • Nanotechnology
  • Parasitology
  • Drug Discovery

Background:

  • African trypanosomiasis (sleeping sickness) and Nagana are caused by Trypanosoma brucei.
  • Current treatments face challenges including toxicity, efficacy, and drug resistance.
  • Novel therapeutic strategies are urgently needed to combat these diseases.

Purpose of the Study:

  • To design and synthesize a new class of synthetic trypanocides using nanostructured DNA-lipid particles.
  • To investigate the mechanism of action and efficacy of these nanoparticles against Trypanosoma brucei.
  • To explore the potential for dual-targeting strategies to mitigate drug resistance.

Main Methods:

  • Self-assembly of core-shell DNA-lipid nanoparticles with hydrophilic DNA shells and hydrophobic lipid cores.
  • Synthesis of DNA-cholesterol nanoparticles for targeted disruption of T. brucei lysosomal membrane integrity.
  • Functionalization of nanoparticle DNA shells with SL-RNA-specific DNAzymes for a dual-targeting approach.

Main Results:

  • DNA-cholesterol nanoparticles demonstrated potent trypanocidal activity, killing T. brucei with nanomolar efficacy.
  • The nanoparticles effectively subverted the membrane integrity of the T. brucei lysosome.
  • A dual-targeting approach using DNAzymes showed potential to reduce the risk of developing drug resistance.

Conclusions:

  • Nanostructured DNA-lipid particles represent a novel and effective class of synthetic trypanocides.
  • Targeting the T. brucei lysosome with DNA-cholesterol nanoparticles offers a promising therapeutic avenue.
  • Programmable nanoparticles with dual-targeting capabilities can enhance efficacy and combat drug resistance in trypanosomiasis treatment.