Autophagy, lithium, and amyotrophic lateral sclerosis

Muscle Nerve. 2009 Aug;40(2):173-94. doi: 10.1002/mus.21423.


In this article we provide an overview of the intersection between amyotrophic lateral sclerosis (ALS) and the autophagy pathway and discuss the potential protective effects of lithium through mechanisms that recruit autophagy and other effects. The autophagy pathway is recruited during motor neuron (MN) death both in vitro and in vivo. Despite a few controversial issues concerning the significance (detrimental/protective) of autophagy in ALS, recent findings indicate a protective role. Lithium in low doses is a well-known autophagy inducer that clears misfolded proteins and altered mitochondria from MNs. Moreover, lithium preserves mitochondria and sustains their genesis. This effect is replicated by rapamycin, which is an autophagy inducer but with a different mechanism from lithium. Lithium also increases the number of Renshaw cells that are affected early during the progression of experimental ALS. Again, lithium has been reported to decrease glial proliferation in the ALS spinal cord and induces sprouting in corticospinal fibers. Muscle Nerve 40: 173-194, 2009.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Humans
  • Lithium Compounds / pharmacology
  • Lithium Compounds / therapeutic use*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Signal Transduction / drug effects


  • Lithium Compounds
  • Neuroprotective Agents