Human molecular genetics

Astrocytic protection of spinal motor neurons but not cortical neurons against loss of Als2/alsin function.

PMID 19304783


Three neurodegenerative diseases affecting upper and/or lower motor neurons have been associated with loss of ALS2/Alsin function: juvenile amyotrophic lateral sclerosis, primary lateral sclerosis and infantile-onset ascending hereditary spastic paralysis. The distinct neuronal vulnerability and the role of glia in these diseases remains, however, unclear. We here demonstrate that alsin-depleted spinal motor neurons can be rescued from defective survival and axon growth by co-cultured astrocytes. The astrocytic rescue is mediated by a soluble protective factor rather than by cellular contact. Cortical neurons are intrinsically as vulnerable to alsin depletion as spinal motor neurons but cannot be rescued by co-cultured astrocytes. To our knowledge, these data provide the first example of non-cell-autonomous glial effects in a recessive form of motor neuron disease and a potential rationale for the higher vulnerability of upper versus lower motor neurons in ALS2/Alsin-linked disorders.