General Information:

Id: 474
Diseases: Amyotrophic lateral sclerosis
Mus musculus
SOD1G93A transgenic mouse, transfected with human SOD1G93A
BTO:0001279 spinal cord
article
Reference: Fornai F et al.(2008) Lithium delays progression of amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U.S.A. 105: 2052-2057 [PMID: 18250315]

Interaction Information:

Comment The treatment of G93A ALS mice with lithium delayed disease onset and duration and augmented the life span.
Formal Description
Interaction-ID: 2203

drug/chemical compound

Lithium

decreases_activity of

disease

Amyotrophic lateral sclerosis

in G93A mutant mice
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Comment Neurons within lamina VII of G93A mice were severely decreased. Lamina VII contains a larger number of interneurons, defined as Renshaw cells. Lithium administration in G93A mice increased the number of neurons, counted in lamina VII.
Formal Description
Interaction-ID: 2204

drug/chemical compound

Lithium

increases_quantity of

tissue/cell line

interneuron

in G93A mutant mice
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Comment Lithium administration in G93A mice reduced ubiquitin, and SOD1 aggregates in motor neurons. SOD1 accumulation was markedly cleared.
Formal Description
Interaction-ID: 2209

drug/chemical compound

Lithium

decreases_quantity of

phenotype

SOD1 protein aggregates

in G93A mutant mice, counted in lamina VII
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Comment Lithium decreased vacuolization and normalized mitochondrial size. Lithium increased the number of normal mitochondria in both WT and G93A mice.
Formal Description
Interaction-ID: 2226

drug/chemical compound

Lithium

decreases_activity of

process

vacuole organization

in mitochondria
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Comment Lithium administration increased the number of autophagic vacuoles as confirmed by autophagy markers, such as beclin or the microtubule-associated protein 1 light chain 3 (LC3).
Formal Description
Interaction-ID: 2232

drug/chemical compound

Lithium

increases_quantity of

cellular component

autophagic vacuole

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Comment Induction of autophagy by lithium was matched by increased expression of PTEN (the phosphatase acting on PIP3) and a marked reduction in the SER473 phosphorylation of Akt.
Formal Description
Interaction-ID: 2233

drug/chemical compound

Lithium

increases_activity of

process

autophagy

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Comment The autophagy inhibitor 3-MA (3-Methyladenine) increased G93A motor neuron (MN) death by 58% compared with NT G93A MN and by 51% compared with lithium-treated G93A MN. 3-MA administration 2h before lithium treatment, the latter could no longer counteract the effects of 3-MA, confirming that lithium neuroprotection occurs, at least partially, through an autophagic route.
Formal Description
Interaction-ID: 2235

drug/chemical compound

3-Methyladenine

increases_activity of

phenotype

motor neuron degeneration

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Comment The autophagy inhibitor 3-MA (3-Methyladenine) increased G93A motor neuron (MN) death by 58% compared with NT G93A MN and by 51% compared with lithium-treated G93A MN. 3-MA administration 2h before lithium treatment, the latter could no longer counteract the effects of 3-MA, confirming that lithium neuroprotection occurs, at least partially, through an autophagic route.
Formal Description
Interaction-ID: 2237

drug/chemical compound

Lithium

decreases_activity of

phenotype

motor neuron degeneration

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