MilliporeSigma
  • Home
  • Search Results
  • Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-β1.

Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-β1.

Stem cell reports (2017-07-18)
Pratibha Tripathi, Natalia Rodriguez-Muela, Joseph R Klim, A Sophie de Boer, Sahil Agrawal, Jackson Sandoe, Claudia S Lopes, Karolyn Sassi Ogliari, Luis A Williams, Matthew Shear, Lee L Rubin, Kevin Eggan, Qiao Zhou
ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease. Astrocytic factors are known to contribute to motor neuron degeneration and death in ALS. However, the role of astrocyte in promoting motor neuron protein aggregation, a disease hallmark of ALS, remains largely unclear. Here, using culture models of human motor neurons and primary astrocytes of different genotypes (wild-type or SOD1 mutant) and reactive states (non-reactive or reactive), we show that reactive astrocytes, regardless of their genotypes, reduce motor neuron health and lead to moderate neuronal loss. After prolonged co-cultures of up to 2 months, motor neurons show increased axonal and cytoplasmic protein inclusions characteristic of ALS. Reactive astrocytes induce protein aggregation in part by releasing transforming growth factor β1 (TGF-β1), which disrupts motor neuron autophagy through the mTOR pathway. These results reveal the important contribution of reactive astrocytes in promoting aspects of ALS pathology independent of genetic influences.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Neurofilament H & M Antibody, phosphorylated, clone NP1, ascites fluid, clone NP1, Chemicon®
Sigma-Aldrich
Monoclonal Anti-S100B antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL2720, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-Choline Acetyltransferase (ChAT) Antibody, serum, Chemicon®
Sigma-Aldrich
Anti-SOD1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-Microtubule-Associated Protein 2 (MAP2) Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-LCN2 Antibody, from rabbit, purified by affinity chromatography