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Updated: Feb 13, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
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Neuronal Cell Death.

Michael Fricker1, Aviva M Tolkovsky1, Vilmante Borutaite1

  • 1Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales , Australia ; Department of Clinical Neurosciences, University of Cambridge , Cambridge , United Kingdom ; Neuroscience Institute, Lithuanian University of Health Sciences , Kaunas , Lithuania ; and Department of Biochemistry, University of Cambridge , Cambridge , United Kingdom.

Physiological Reviews
|March 1, 2018
PubMed
Summary
This summary is machine-generated.

Neurons have over a dozen ways to die, complicating treatments for neurological diseases. Understanding these diverse neuronal death mechanisms is crucial for developing effective therapies for conditions like stroke and Alzheimer's disease.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Neuronal cell death is critical during development and disease due to limited neuron regeneration.
  • Historically, neuronal death was categorized simply, but over a dozen distinct mechanisms are now recognized.
  • Non-neuronal cells also significantly contribute to neuronal demise.

Purpose of the Study:

  • To review the diverse mechanisms of neuronal cell death.
  • To explore triggers of neuronal death in development and disease.
  • To reassess neuronal death in stroke and Alzheimer's disease and discuss therapeutic implications.

Main Methods:

  • Comprehensive literature review of neuronal cell death pathways.
  • Analysis of developmental and pathological triggers of neuronal death.
  • Re-evaluation of cell death mechanisms in major neurological diseases.

Main Results:

  • Detailed review of numerous neuronal death pathways including apoptosis, necroptosis, ferroptosis, pyroptosis, and others.
  • Identification of diverse inducers: axotomy, excitotoxicity, protein aggregation, inflammation, and more.
  • Analysis of neuronal death in stroke and Alzheimer's, highlighting complexity and overlap.

Conclusions:

  • Neuronal death is multifaceted, involving at least a dozen distinct pathways.
  • Pinpointing specific death mechanisms in pathology is challenging due to molecular overlap.
  • Understanding these complex pathways is vital for developing targeted neuroprotective therapies.