Autophagy dysregulation in cell culture and animals models of spinal muscular atrophy

Sara K. Custer, Elliot Androphy

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Abnormal autophagy has become a central thread linking neurodegenerative diseases, particularly of the motor neuron. One such disease is spinal muscular atrophy (SMA), a genetic neuromuscular disorder caused by mutations in the SMN1 gene resulting in low levels of Survival Motor Neuron (SMN) protein. Despite knowing the causal protein, the exact intracellular processes that are involved in the selective loss of motor neurons remain unclear. Autophagy induction can be helpful or harmful depending on the situation, and we sought to understand the state of the autophagic response in SMA. We show that cell culture and animal models demonstrate induction of autophagy accompanied by attenuated autophagic flux, resulting in the accumulation of autophagosomes and their associated cargo. Expression of the SMN-binding protein a-COP, a known modulator of autophagic flux, can ameliorate this autophagic traffic jam.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume61
DOIs
StatePublished - 2014

Fingerprint

Spinal Muscular Atrophy
Autophagy
Motor Neurons
Animal Models
Cell Culture Techniques
Inborn Genetic Diseases
Neurodegenerative Diseases
Carrier Proteins
Proteins
Mutation
Genes

Keywords

  • Autophagy
  • Motor neuron
  • Spinal muscular atrophy
  • Survival motor neuron

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Medicine(all)

Cite this

Autophagy dysregulation in cell culture and animals models of spinal muscular atrophy. / Custer, Sara K.; Androphy, Elliot.

In: Molecular and Cellular Neuroscience, Vol. 61, 2014, p. 133-140.

Research output: Contribution to journalArticle

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