The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons.
Ilaria Tonazzini, Geeske M Van Woerden, Cecilia Masciullo and 3 others
PMID 31798818WHAT IT FOUND
Mouse neurons lacking the protein under study misaligned on grooved surfaces.
Low-dose nocodazole improved alignment and reduced extra branching; replacing the protein only partly helped. This is a cell mechanism finding, not a tested therapy for patients.
Key findings
01Neurons lacking the protein showed poorer axonal alignment on grooved substrates than wild-type neurons.
02Low-dose nocodazole improved axonal alignment and reduced excessive secondary axonal branching in deficient neurons.
03Replacing the protein only partially rescued axonal alignment in deficient neurons.
STILL TO COME
How it was doneWhat they found
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What it does not show
All experiments were done in mouse hippocampal neurons grown on artificial grooved surfaces, so the study does not show what happens in people with Angelman syndrome or Dup15q syndrome. Nocodazole and blebbistatin were tested only on cells, not in patients, so no clinical dose, safety, or benefit can be inferred. Reinstating the protein only partially corrected axonal guidance, and nocodazole also impaired alignment in normal neurons. The study did not measure speech, motor, cognitive, or behavioural outcomes.
Declared interests
The supplied funding sentence names Nederlandse Organisatie voor Wetenschappelijk Onderzoek, MSCA IF, and Fondazione Umberto Veronesi as funders.
The easy way to misread this
Do not conclude that nocodazole or protein replacement is a treatment for Angelman syndrome or autism. The rescue was observed only in mouse neurons grown on artificial grooved surfaces, and the paper states its relevance to Angelman syndrome pathophysiology still needs to be established.