Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs.

Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy

BOIDO, Marina Maria
First
;
VERCELLI, Alessandro
2016-01-01

Abstract

Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs.
2016
10
1
10
Motor neuron disease, endplate, denervation, immaturity, neurofilament, therapy
Marina, Boido; Alessandro, Vercelli
File in questo prodotto:
File Dimensione Formato  
Boido and Vercelli Front Neuroanat 2016.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 822.08 kB
Formato Adobe PDF
822.08 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1556650
Citazioni
  • ???jsp.display-item.citation.pmc??? 30
  • Scopus 45
  • ???jsp.display-item.citation.isi??? 44
social impact