Neuroprotective effect of CuATSM on neurotoxin-induced motor neuron loss in an ALS mouse model.

Neuroprotective effect of CuATSM on neurotoxin-induced motor neuron loss in an ALS mouse model.

Publication date: Jun 07, 2019

CuATSM is a PET-imaging agent that has recently received attention for its success in extending the lifespan in animals in several neurodegenerative disease models. In the SOD1 model of ALS, CuATSM prolonged mouse longevity far longer than any previously tested therapeutic agents. The mechanism underlying this outcome has not been fully understood, but studies suggest that this copper complex contributes to maintaining copper homeostasis in mitochondria. More specifically for the SOD1 model, the molecule supplies copper back to the SOD1 protein. Additionally, CuATSM demonstrated similar protective effects in various in vivo Parkinson’s disease mouse models. In the current pilot study, we utilized a neurodegenerative mouse model of motor neuron degeneration induced by the neurotoxin β-sitosterol β-D-glucoside. In this model, slow but distinct and progressive features of sporadic ALS occur. Treatment with CuATSM kept animal behavioural performance on par with the controls and prevented the extensive motor neuron degeneration and microglia activation seen in the untreated animals. These outcomes support a broader neuroprotective role for CuATSM beyond mutant SOD models of ALS.

Kuo, M.T.H., Beckman, J.S., and Shaw, C.A. Neuroprotective effect of CuATSM on neurotoxin-induced motor neuron loss in an ALS mouse model. 21107. 2019 Neurobiol Dis.

Concepts Keywords
ALS Imaging
Copper ALS
Glucoside Organ systems
Homeostasis Nervous system
Imaging Agent Neurological disorders
Longevity Metalloproteins
Microglia Oxidoreductases
Mitochondria Motor neuron diseases
Molecule SOD1
Motor Neuron Neurodegeneration
Mutant Amyotrophic lateral sclerosis
Neurodegenerative Neuroprotection
Neuroprotective Neurotoxin
Neurotoxin
Parkinson
Progressive
Protein
Sitosterol
SOD1
Vivo

Semantics

Type Source Name
disease MESH Amyotrophic lateral sclerosis
disease DOID SOD
gene UNIPROT JTB
gene UNIPROT NR1I2
drug DRUGBANK beta-Sitosterol
disease MESH neuron degeneration
gene UNIPROT EGR3
pathway BSID Copper homeostasis
drug DRUGBANK Copper
disease DOID neurodegenerative disease
disease MESH neurodegenerative disease
drug DRUGBANK Spinosad
gene UNIPROT SOD1
gene UNIPROT IGFALS
disease DOID ALS

Original Article

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