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Lysosomotropic Drugs: Pharmacological Tools to Study Lysosomal Function.

Sandra Pisonero-Vaquero1, Diego Luis Medina1

  • 1Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy.

Current Drug Metabolism
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Summary

Lysosomotropic drugs accumulate in lysosomes, causing effects similar to lysosomal storage disorders (LSDs). These drugs offer valuable models for studying LSDs and their underlying mechanisms.

Keywords:
LSDsLysosomotropismTFEBautophagylysosomal functionlysosomephospholipidosis

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Area of Science:

  • Cell Biology
  • Pharmacology
  • Genetics

Background:

  • Lysosomotropic molecules are internalized by lysosomes, impacting cellular processes.
  • Many clinically used drugs exhibit lysosomotropic properties, leading to effects like phospholipidosis.
  • The precise pathophysiological role of lysosomotropism remains incompletely understood.

Purpose of the Study:

  • To review the effects of lysosomotropic drugs on lysosomal functions.
  • To compare these drug-induced effects with the phenotypic characteristics of lysosomal storage disorders (LSDs).

Main Methods:

  • Literature review of studies on lysosomotropic agents and lysosomal functions.
  • Comparative analysis of drug-induced lysosomal alterations and LSD phenotypes.

Main Results:

  • Lysosomotropic drugs induce lysosomal changes, including vacuolization and enzyme inhibition.
  • These drug-induced changes mimic key pathological features observed in LSDs.
  • Accumulation of undegraded material is a common consequence of lysosomotropic drug action.

Conclusions:

  • Drug-induced lysosomal effects closely resemble pathological features of human LSDs.
  • Lysosomotropic drugs serve as valuable tools for investigating LSD mechanisms.
  • These agents can be utilized to develop pharmacologically induced models of LSDs.