The prominent causes for motor neuron diseases like ALS are demyelination, 
immune dysregulation, and neuroinflammation. Numerous research studies indicate 
that the downregulation of IGF-1 and GLP-1 signaling pathways plays a 
significant role in the progression of ALS pathogenesis and other neurological 
disorders. In the current review, we discussed the dysregulation of IGF-1/GLP-1 
signaling in neurodegenerative manifestations of ALS like a genetic anomaly, 
oligodendrocyte degradation, demyelination, glial overactivation, immune 
deregulation, and neuroexcitation. In addition, the current review reveals the 
IGF-1 and GLP-1 activators based on the premise that the restoration of abnormal 
IGF-1/GLP-1 signaling could result in neuroprotection and neurotrophic effects 
for the clinical-pathological presentation of ALS and other brain diseases. 
Thus, the potential benefits of IGF-1/GLP-1 signal upregulation in the 
development of disease-modifying therapeutic strategies may prevent ALS and 
associated neurocomplications.