Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis.

Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis. Exp Neurol. 2018 Jun 19;: Authors: Shijo T, Warita H, Suzuki N, Ikeda K, Mitsuzawa S, Akiyama T, Ono H, Nishiyama A, Izumi R, Kitajima Y, Aoki M Abstract Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterized by the systemic loss of motor neurons with prominent astrocytosis and microgliosis in the spinal cord and brain. Astrocytes play an essential role in maintaining extracellular microenvironments that surround motor neurons, and are activated by various insults. Growing evidence points to a non-cell autonomous neurotoxicity caused by chronic and sustained astrocytic activation in patients with neurodegenerative diseases, including ALS. However, the mechanisms that underlie the harmful effects of astrocytosis in patients with ALS remain unresolved. We focused on bone morphogenetic proteins as a major soluble factor that promotes astrocytogenesis and its activation in the adult spinal cord. In a transgenic rat model with ALS-linked mutant Cu/Zn superoxide dismutase gene, BMP4 was progressively up-regulated in reactive astrocytes of the spinal ventral horns, whereas the BMP-antagonist noggin was decreased in association with neuronal degeneration. Continuous intrathecal noggin supplementation after disease onset significantly ameliorated motor dysfunction symptoms, ne...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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