Presymptomatic activation of the PDGF-CC pathway accelerates onset of ALS neurodegeneration.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown origins. Neurodegeneration in ALS mouse models occurs together with signs of disrupted blood-spinal cord barrier (BSCB) and regressed capillary network, but the molecular pathways contributing to these vascular pathologies remain unknown. We show that motor neurons of human sporadic ALS patients (n = 12) have increased gene expression of PDGFC and its activator PLAT and presymptomatic activation of the PDGF-CC pathway in SOD1 (G93A) mice leads to BSCB dysfunction. Decrease of Pdgfc expression in SOD1 (G93A) mice restored vascular barrier properties, reduced motor neuron loss and delayed symptom onset by up to 3 weeks. Similarly, lower expression levels of PDGFC or PLAT in motor neurons of sporadic ALS pat

SUBMITTER: Lewandowski SA 

PROVIDER: S-EPMC4839168 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature