Affordable Access

deepdyve-link
Publisher Website

Synaptotagmin 13 is neuroprotective across motor neuron diseases

Authors
  • Nizzardo, M.1, 2
  • Taiana, M.1
  • Rizzo, F.1, 2
  • Aguila Benitez, J.3
  • Nijssen, J.3
  • Allodi, I.3
  • Melzi, V.1
  • Bresolin, N.1, 2
  • Comi, G. P.1, 4
  • Hedlund, E.3
  • Corti, S.1, 2
  • 1 University of Milan,
  • 2 Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
  • 3 Karolinska Institutet,
  • 4 Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Diseases Unit, Via Francesco Sforza 35, 20122 Milan, Italy
Type
Published Article
Journal
Acta Neuropathologica
Publisher
Springer-Verlag
Publication Date
Feb 17, 2020
Volume
139
Issue
5
Pages
837–853
Identifiers
DOI: 10.1007/s00401-020-02133-x
PMID: 32065260
PMCID: PMC7181443
Source
PubMed Central
License
Unknown

Abstract

In amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), spinal and lower brainstem motor neurons degenerate, but some motor neuron subtypes are spared, including oculomotor neurons (OMNs). The mechanisms responsible for this selective degeneration are largely unknown, but the molecular signatures of resistant and vulnerable motor neurons are distinct and offer clues to neuronal resilience and susceptibility. Here, we demonstrate that healthy OMNs preferentially express Synaptotagmin 13 (SYT13) compared to spinal motor neurons. In end-stage ALS patients, SYT13 is enriched in both OMNs and the remaining relatively resilient spinal motor neurons compared to controls. Overexpression of SYT13 in ALS and SMA patient motor neurons in vitro improves their survival and increases axon lengths. Gene therapy with Syt13 prolongs the lifespan of ALS mice by 14% and SMA mice by 50% by preserving motor neurons and delaying muscle denervation. SYT13 decreases endoplasmic reticulum stress and apoptosis of motor neurons, both in vitro and in vivo. Thus, SYT13 is a resilience factor that can protect motor neurons and a candidate therapeutic target across motor neuron diseases. Electronic supplementary material The online version of this article (10.1007/s00401-020-02133-x) contains supplementary material, which is available to authorized users.

Report this publication

Statistics

Seen <100 times