Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice

Mòdol‐Caballero, Guillem; Herrando-Grabulosa, Mireia; García-Lareu, Belén; Solanes, Neus; Verdés, Sergi; Osta, Rosario; Calvo, Ana C.; Bosch, Assumpció; Navarro, Xavier

doi:10.1016/j.nbd.2020.104793

Cited by 17 publications

(27 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, their research also found that the loss of NRG1 expression and C-boutons occurred almost contemporaneously and the expressions of ErbB3 and ErbB4 were reduced in the motor neurons of SOD1-muted ALS mice. Mòdol-Caballero et al (2020) also found that NRG1 expression was reduced in both ALS patients and the SOD1-mutated ALS mouse model. Overexpression of type III NRG1 can preserve the neuromuscular function of the hindlimbs, improve locomotor performance, increase the number of surviving motoneurons, and reduce glial reactivity in the treated female SOD1 mice.…”

Section: Neuregulins In Other Neurodegenerative Diseasesmentioning

confidence: 79%

Neuregulins in Neurodegenerative Diseases

Lin

Zhao

2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), are typically characterized by progressive neuronal loss and neurological dysfunctions in the nervous system, affecting both memory and motor functions. Neuregulins (NRGs) belong to the epidermal growth factor (EGF)-like family of extracellular ligands and they play an important role in the development, maintenance, and repair of both the central nervous system (CNS) and peripheral nervous system (PNS) through the ErbB signaling pathway. They also regulate multiple intercellular signal transduction and participate in a wide range of biological processes, such as differentiation, migration, and myelination. In this review article, we summarized research on the changes and roles of NRGs in neurodegenerative diseases, especially in AD. We elaborated on the structural features of each NRG subtype and roles of NRG/ErbB signaling networks in neurodegenerative diseases. We also discussed the therapeutic potential of NRGs in the symptom remission of neurodegenerative diseases, which may offer hope for advancing related treatment.

show abstract

Section: Neuregulins In Other Neurodegenerative Diseasesmentioning

confidence: 79%

Neuregulins in Neurodegenerative Diseases

Lin

Zhao

2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…At the postsynaptic side, genetic and most importantly, antibody‐mediated activation of MuSK prevents NMJ denervation in a model of amyotrophic lateral sclerosis (Cantor et al ., 2018). Also, muscle overexpression of Dok7 (Miyoshi et al ., 2017) or Neuregulin‐1 (Modol‐Caballero et al ., 2020) through a gene therapy approach has shown important protective responses in animal models of the same disease. From a clinical viewpoint, these studies show that manipulation of NMJ postsynaptic proteins could result in a significant improvement in the quality of life of patients with amyotrophic lateral sclerosis. An additional important goal of possible therapeutic interventions is to maximize the chances that local positive effects on NMJ regeneration will not be accompanied by undesired side effects in other body regions.…”

Section: Discussionmentioning

confidence: 99%

“…A single antibody injection at early symptomatic stage (P90) resulted in significantly delayed denervation at P110 in hSOD1‐G93A mice; moreover, chronic antibody delivery resulted in improved motor performance and decreased motor neuron loss in amyotrophic lateral sclerosis model mice (Cantor et al ., 2018). Remarkably, recent studies have shown that the overexpression of Dok7 (Miyoshi et al ., 2017) or Neuregulin‐1 (Modol‐Caballero et al ., 2020) by an adeno‐associated virus approach in skeletal muscles at pre‐symptomatic stages of hSOD1‐G93A mice has important protective effects, including delayed NMJ denervation, improved motor function and, consequently, muscle fibre atrophy suppression accompanied by improved coordination and motor performance (Miyoshi et al ., 2017; Modol‐Caballero et al ., 2020).…”

Section: Cellular and Molecular Clues In The Maintenance Of The Nmj Pmentioning

confidence: 99%

Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse

et al. 2020

View full text Add to dashboard Cite

The coordinated movement of many organisms relies on efficient nerve–muscle communication at the neuromuscular junction (NMJ), a peripheral synapse composed of a presynaptic motor axon terminal, a postsynaptic muscle specialization, and non‐myelinating terminal Schwann cells. NMJ dysfunctions are caused by traumatic spinal cord or peripheral nerve injuries as well as by severe motor pathologies. Compared to the central nervous system, the peripheral nervous system displays remarkable regenerating abilities; however, this capacity is limited by the denervation time frame and depends on the establishment of permissive regenerative niches. At the injury site, detailed information is available regarding the cells, molecules, and mechanisms involved in nerve regeneration and repair. However, a regenerative niche at the final functional step of peripheral motor innervation, i.e. at the mature neuromuscular synapse, has not been deciphered. In this review, we integrate classic and recent evidence describing the cells and molecules that could orchestrate a dynamic ecosystem to accomplish successful NMJ regeneration. We propose that such a regenerative niche must ensure at least two fundamental steps for successful NMJ regeneration: the proper arrival of incoming regenerating axons to denervated postsynaptic muscle domains, and the resilience of those postsynaptic domains, in morphological and functional terms. We here describe and combine the main cellular and molecular responses involved in each of these steps as potential targets to help successful NMJ regeneration.

show abstract

“…Indeed, NRG1 was shown to activate cell survival pathways in muscles and the spinal cord, protecting against denervation, neuroinflammation, and motor neuron loss. As the NMJs were preserved, treated mice had better neuromuscular and motor functions [52].…”

Section: Genetic Interventionsmentioning

confidence: 99%

Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?

Scaricamazza

Salvatori

Ferri

et al. 2021

Cells

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective degeneration of upper and lower motor neurons and by the progressive weakness and paralysis of voluntary muscles. Despite intense research efforts and numerous clinical trials, it is still an incurable disease. ALS had long been considered a pure motor neuron disease; however, recent studies have shown that motor neuron protection is not sufficient to prevent the course of the disease since the dismantlement of neuromuscular junctions occurs before motor neuron degeneration. Skeletal muscle alterations have been described in the early stages of the disease, and they seem to be mainly involved in the “dying back” phenomenon of motor neurons and metabolic dysfunctions. In recent years, skeletal muscles have been considered crucial not only for the etiology of ALS but also for its treatment. Here, we review clinical and preclinical studies that targeted skeletal muscles and discuss the different approaches, including pharmacological interventions, supplements or diets, genetic modifications, and training programs.

show abstract

Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice

Cited by 17 publications

References 63 publications

Neuregulins in Neurodegenerative Diseases

Neuregulins in Neurodegenerative Diseases

Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse

Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?

Contact Info

Product

Resources

About