Proprioceptive synaptic dysfunction is a key feature in mice and humans with spinal muscular atrophy.

ABSTRACT: Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by a varying degree of severity that is correlated with the reduction of SMN protein levels. Motor neuron degeneration and skeletal muscle atrophy are hallmarks of SMA, but it is unknown whether other mechanisms contribute to the spectrum of clinical phenotypes. Here, through a combination of physiological and morphological studies in mouse models and SMA patients, we identify dysfunction and loss of proprioceptive sensory synapses as key signatures of SMA pathology. We demonstrate that type 3 SMA patients exhibit impaired proprioception and that their proprioceptive synapses are dysfunctional as measured by the neurophysiological test of the Hoffmann reflex. We also show moderate loss of spinal motor neurons along

SUBMITTER: Simon CM 

PROVIDER: S-EPMC12416786 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature