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Mol Cell Neurosci. 2014 Jul;61:133-40. doi: 10.1016/j.mcn.2014.06.006. Epub 2014 Jun 28.

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

Author information

1
Indiana University School of Medicine, Department of Dermatology, Walther Hall, R3 C636, Indianapolis, IN 46202, United States.
2
Indiana University School of Medicine, Department of Dermatology, Walther Hall, R3 C636, Indianapolis, IN 46202, United States. Electronic address: eandro@iu.edu.

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.

KEYWORDS:

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

PMID:
24983518
PMCID:
PMC4135029
DOI:
10.1016/j.mcn.2014.06.006
[Indexed for MEDLINE]
Free PMC Article

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