Related Experiment Video

Updated: Feb 6, 2026

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS
06:49

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

Published on: October 6, 2015

20.9K

Parkin is a disease modifier in the mutant SOD1 mouse model of ALS

Gloria M Palomo1, Veronica Granatiero1, Hibiki Kawamata1

  • 1Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

EMBO Molecular Medicine
|August 22, 2018
PubMed

Insights

Mutant SOD1 in ALS triggers mitochondrial damage and mitophagy. Unexpectedly, inhibiting Parkin, a key mitophagy protein, slows ALS progression by preserving mitochondrial function and biogenesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • Mutant copper/zinc superoxide dismutase (SOD1) is implicated in motor neuron death in amyotrophic lateral sclerosis (ALS).
  • Mitochondrial damage triggers cellular quality control, including mitophagy, to remove dysfunctional mitochondria.

Purpose of the Study:

  • To investigate the role of Parkin-mediated mitophagy in SOD1-G93A mouse models of ALS.
  • To determine if Parkin activity influences disease progression and motor neuron survival in ALS.

Main Methods:

  • Analysis of spinal cord tissue from SOD1-G93A mice.
  • Assessment of mitophagy markers, mitochondrial dynamics proteins (Miro1, Mfn2), and PGC1α levels.
  • Evaluation of disease progression and survival in Parkin-ablated SOD1-G93A mice.

Main Results:

  • Mitophagy is activated in SOD1-G93A mice, with p62 recruitment to mitochondria.
  • Parkin, Miro1, Mfn2, and PGC1α are depleted in SOD1-G93A mice.
  • Parkin genetic ablation significantly delays disease progression, prolongs survival, and preserves motor neurons and muscle innervation.

Conclusions:

  • Parkin-mediated mitophagy exacerbates ALS pathology by depleting mitochondrial dynamics proteins and inhibiting biogenesis.
  • Parkin acts as a disease modifier in ALS, suggesting therapeutic potential in modulating mitophagy pathways.
Keywords:
ParkinSOD1amyotrophic lateral sclerosismitochondria quality controlmitophagy

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