Zebrafish Model of Amyotrophic Lateral Sclerosis 

 

 

Background: Amyotrophic lateral sclerosis (ALS) also called as a motor neuron disease is characterized by the presence of inclusion bodies in the cytoplasm of motor neurons. A number of pathological proteins have been associated with the inclusion bodies namely TDP-43, MST1, SOD1, FUS, and C9orf72.

 

Pentagrit zebrafish model of amyotrophic lateral sclerosis is able to replicate the death of pyramidal neurons in the motor cortex and motor neurons in the brain stem and central spinal environment. Eventually the animal develops muscle atrophy with symptoms initiating with stiff muscles and muscle twitching, affecting activities such as swallowing, and breathing. Pathological hallmarks includes the sclerosis of the corticospinal and corticobulbar tracts with thinning of the hypoglossal nerves and anterior roots of the spinal cord.

 

Neuropathologic analysis of zebrafish model of ALS is also indicated by accumulation of ubiquitinated inclusions in the brain and spinal cord. This is also concomitant with a reduction in the number of hippocampal neurons. Upon staining of the brain there is a marked reduction in the  staining of TAR-DNA binding protein 43 in the nucleus. These events leads to the formation of  ubiquitin inclusions in the cytoplasm of spinal motor neurons of zebrafish model of Amyotrophic lateral sclerosis. 

 

Riluzole the first treatment for amyotrophic lateral sclerosis to approved by the U.S. Food and Drug Administration employed as a comparator shows neuroprotective and rescue of motor activity of zebrafish model of ALS. Similarly edarvone as a comparator rescues oxidative stress driven degeneration of both motor neurons and skeletal muscles in our zebrafish model of amyotrophic lateral sclerosis

Dose Efficacy Patterns identified with Zebrafish model of ALS Accelerate Candidate Decision Making

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