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Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.

Daniele Arosio1, Carlo Musio1

  • 1Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 38123 Trento, Italy.

Life (Basel, Switzerland)
|September 27, 2025
PubMed
Summary
This summary is machine-generated.

Neuronal chloride homeostasis is crucial for brain function. Disruptions in chloride balance are linked to epilepsy, Alzheimer

Keywords:
Alzheimer’s diseaseClCGABA signalingHuntington’s diseaseNKCC(1)/KCC(2)autism spectrum disorderbrain diseaseschloride homeostasisepilepsyneurological disordersprecision medicinetherapeutic targets

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathophysiology

Background:

  • Neuronal chloride (Cl-) homeostasis is essential for normal brain function.
  • Disruptions in chloride balance are increasingly implicated in various neurological disorders.

Purpose of the Study:

  • To review and synthesize evidence on the role of chloride dysregulation in neurological diseases.
  • To explore the potential of targeting chloride transporters as a therapeutic strategy.

Main Methods:

  • Integration of preclinical models and clinical studies.
  • Utilized electrophysiology, molecular analyses, and advanced imaging (e.g., ClopHensor).
  • Incorporated behavioral assays and subcellular chloride imaging.

Main Results:

  • Identified distinct chloride dysregulation patterns in epilepsy, Alzheimer's disease, autism spectrum disorders, and Huntington's disease.
  • Demonstrated KCC2 downregulation in epilepsy and Alzheimer's disease models.
  • Showcased NKCC1/KCC2 ratio alterations in autism spectrum disorders and striatal imbalances in Huntington's disease.

Conclusions:

  • Chloride homeostasis is a critical biomarker and therapeutic target for neurological disorders.
  • Therapeutic strategies targeting chloride transporters show preclinical promise.
  • Precision medicine approaches are needed to address the heterogeneity of chloride dysregulation.