NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

Casas, Caty

doi:10.3390/cells9040808

Cited by 11 publications

(11 citation statements)

References 54 publications

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“…Probably, the controversy of whether to boost autophagy is not the issue to tackle, but its fine-tune activation may yield protective effects. Indeed, we have recently reported that NeuroHeal-fine-tuned autophagy promotes neuroprotection of neonatal motoneurons, improves motor axonal regeneration, and has a role in neuropathic pain [20,[56][57][58].…”

Section: Discussionmentioning

confidence: 99%

NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy

Marmolejo-Martínez-Artesero

Mañas-García

Barreiro

et al. 2020

Cells

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Muscle wasting is an unmet medical need which leads to a reduction of myofiber diameter and a negative impact on the functional performance of daily activities. We previously found that a new neuroprotective drug called NeuroHeal reduced muscle atrophy produced by transient denervation. Aiming to decipher whether NeuroHeal has a direct role in muscle biology, we used herein different models of muscle atrophy: one caused by chronic denervation, another caused by hindlimb immobilization, and lastly, an in vitro model of myotube atrophy with Tumor Necrosis Factor-α (TNFα). In all these models, we observed that NeuroHeal reduced muscle atrophy and that SIRT1 activation seems to be required for that. The treatment downregulated some critical markers of protein degradation: Muscle Ring Finger 1 (MuRF1), K48 poly-Ub chains, and p62/SQSTM1. Moreover, it seems to restore the autophagy flux associated with denervation. Hence, we envisage a prospective use of NeuroHeal at clinics for different myopathies.

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Section: Discussionmentioning

confidence: 99%

NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy

Marmolejo-Martínez-Artesero

Mañas-García

Barreiro

et al. 2020

Cells

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“…Neuropeptides are key regulators of peripheral nociception and contribute to the mechanisms regulating central sensitisation to pain. In many cases, chronic inflammation, ion channel imbalance and a lack of inhibition in the dorsal horn of the spinal cord partake in maintaining pain sensation [182]. PACAP and VIP are expressed across key anatomical regions/structures that are important in somatosensory processing and the transmission of pain signals [183].…”

Section: Neuropathic Painmentioning

confidence: 99%

“…The overlap between pain and inflammatory signalling has been extensively studied and reviewed [189]. Addition-ally, an association between axonal regeneration and pain has been hypothesised, with evidence suggesting that accelerated regeneration may ameliorate pain of nerve origin [182]. PACAP and VIP have well-described roles in promoting axonal regeneration after peripheral nerve injury [34,191].…”

Section: Neuropathic Painmentioning

confidence: 99%

Targeting the neurological comorbidities of multiple sclerosis: the beneficial effects of VIP and PACAP neuropeptides

Jansen¹,

Broome²,

Castorina³

2022

J. Integr. Neurosci.

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Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclaseactivating polypeptide (PACAP) are two widely expressed neuropeptides with important immunomodulatory and neuroprotective properties in the central nervous system (CNS). Both VIP and PACAP have been implicated in several neurological diseases and have shown favourable e fects in di ferent animal models of multiple sclerosis (MS). MS is a chronic in lammatory and neurodegenerative disease of the CNS a fecting over 2.5 million people worldwide. The disease is characterised by extensive neuroin lammation, demyelination and axonal loss. Currently, there is no cure for MS, with treatment options only displaying partial e ficacy. Importantly, epidemiological studies in the MS population have demonstrated that there is a high incidence of neurological and psychological comorbidities such as depression, anxiety, epilepsy and stroke among a licted people. Hence, given the widespread protective e fects of the VIP/PACAP system in the CNS, this review will aim at exploring the beneficial roles of VIP and PACAP in ameliorating some of the most common neurological comorbidities associated with MS. The final scope of the review is to put more emphasis on how targeting the VIP/PACAP system may be an e fective therapeutic strategy to modify MS disease course and its associated comorbidities.

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“…Drug repurposing for other indications facilitates its readiness for clinical use, since their PD and PK are well-known in humans. We have previously reported its neuroprotective effects in different neurodegenerative models [ 12 , 14 , 15 , 16 ]. In addition, we recently observed that NeuroHeal protects the muscle by reducing atrophy induced by denervation or by immobilization [ 17 ], suggesting it may have also protective effects in other types of myopathies.…”

Section: Introductionmentioning

confidence: 99%

NeuroHeal Improves Muscle Regeneration after Injury

Marmolejo-Martínez-Artesero

Venegas

Marotta

et al. 2020

Cells

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Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.

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NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

Cited by 11 publications

References 54 publications

NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy

NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy

Targeting the neurological comorbidities of multiple sclerosis: the beneficial effects of VIP and PACAP neuropeptides

NeuroHeal Improves Muscle Regeneration after Injury

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