Transmission-selective muscle pathology induced by the active propagation of mutant huntingtin across the human neuromuscular synapse.

ABSTRACT: Neuron-to-neuron transmission of aggregation-prone, misfolded proteins may potentially explain the spatiotemporal accumulation of pathological lesions in the brains of patients with neurodegenerative protein-misfolding diseases (PMDs). However, little is known about protein transmission from the central nervous system to the periphery, or how this propagation contributes to PMD pathology. To deepen our understanding of these processes, we established two functional neuromuscular systems derived from human iPSCs. One was suitable for long-term high-throughput live-cell imaging and the other was adapted to a microfluidic system assuring that connectivity between motor neurons and muscle cells was restricted to the neuromuscular junction. We show that the Huntington's disease (HD)-associated

SUBMITTER: Dinamarca MC 

PROVIDER: S-EPMC10791992 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature