BioProject

Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. More...

Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155. Overall design: Total RNA was isolated from whole spinal cord homogenate - post mortem obtained from healthy donors without known neurologic diseases and from sALS and fALS donors. Total RNA was extracted using mirVanaTM miRNA isolation kit (Ambion) according to the manufacturer’s protocol. nCounter Nanostring custom MG447 human microglia chip was used for gene expression profile Less...