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Mapping Lysosomal Storage Disorders with Neurological Features by Cellular Pathways: Towards Precision Medicine.

Anna Makridou1, Evangelie Sintou1, Sofia Chatzianagnosti1

  • 1Department of Histology-Embryology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Current Issues in Molecular Biology
|January 30, 2026
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Summary

Lysosomal storage disorders (LSDs) are inherited metabolic diseases impairing cell function. A new cellular-pathway framework aids in classifying neurological LSDs and developing personalized treatments.

Keywords:
autophagybiogenesis and signalingcross-organelle interactionsenzymatic hydrolytic defectslysosomal storage disordersneurological involvementprecision medicineprogressive neurological symptomstransporter-related defects

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Area of Science:

  • Biochemistry
  • Genetics
  • Cell Biology

Background:

  • Lysosomal storage disorders (LSDs) are inherited metabolic diseases caused by impaired lysosomal function.
  • Traditional classification by stored macromolecule doesn't reflect underlying molecular mechanisms.
  • Neurological impairment is common in LSDs due to high metabolic demands and clearance issues.

Purpose of the Study:

  • To propose a cellular-pathway-oriented framework for classifying LSDs with neurological features.
  • To highlight how this framework can guide personalized therapeutic strategies for neurological LSDs.

Main Methods:

  • Review of recent advances in genetics and cell biology.
  • Functional classification of LSDs based on disrupted lysosomal pathways.
  • Analysis of genomic technologies and multi-omics platforms.

Main Results:

  • Shift from substrate-based to functional classification of LSDs.
  • Identification of key pathways disrupted in LSDs: enzymatic, transporter, biogenesis, and cross-organelle interactions.
  • Genomic and multi-omics data facilitate earlier diagnosis and tailored therapies.

Conclusions:

  • A cellular-pathway framework offers a better understanding of LSD complexity.
  • This approach provides a roadmap for precision medicine in neurological LSDs.
  • Personalized therapeutic strategies are informed by this classification system.