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Neuroprotective effect of the PACAP-ADNP axis on SOD1G93A mutant motor neuron death induced by trophic factors deprivation

Magrì, Benedetta, D'Amico, Agata Grazia, Maugeri, Grazia, Morello, Giovanna, La Cognata, Valentina, Saccone, Salvatore, Federico, Concetta, Cavallaro, Sebastiano, D'Agata, Velia·2023·Neuropeptides
DOI 10.1016/j.npep.2023.102386
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Abstract

Amyotrophic lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons in the central nervous system. Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for approximately in 20% of familial ALS cases. The pathological mechanisms underlying the toxicity induced by mutated SOD1 are still unknown. However, it has been hypothesized that oxidative stress (OS) has a crucial role in motor neuron degeneration in ALS patients. Moreover, it has been described that SOD1 mutation interferes expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a protective key modulator against OS and reactive oxygen species (ROS) formation. The protective effect of pituitary adenylate cyclase-activating peptide (PACAP) has been demonstrated in various neurological disorders, including ALS. Some of its effects are mediated by the stimulation of an intracellular factor known as activity-dependent protein (ADNP). The role of PACAP-ADNP axis on mutated SOD1 motor neuron degeneration has not been explored, yet. The present study aimed to investigate whether PACAP prevented apoptotic cell death induced by growth factor deprivation through ADNP activation and whether the peptidergic axis can counteract the OS insult. By using an in vitro model of ALS, we demonstrated that PACAP by binding to PAC1 receptor (PAC1R) prevented motor neuron death induced by serum deprivation through induction of the ADNP expression via PKC stim…

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Authors
Magrì, B., D'Amico, A. G., Maugeri, G., Morello, G., La Cognata, V., Saccone, S., Federico, C., Cavallaro, S., & D'Agata, V.
Venue
Neuropeptides
Publisher
Elsevier BV
Published
2023-12
Volume
102
Pages
102386
ISSN
0143-4179
DOI
10.1016/j.npep.2023.102386
Cited by
3
References
1
Language
en
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CoChat. (2026). Citation check: Neuroprotective effect of the PACAP-ADNP axis on SOD1G93A mutant motor neuron death induced by trophic factors deprivation. https://app.cochat.ai/papers/10.1016/j.npep.2023.102386
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Magrì, B., D'Amico, A. G., Maugeri, G., Morello, G., La Cognata, V., Saccone, S., Federico, C., Cavallaro, S., & D'Agata, V. (2023). Neuroprotective effect of the PACAP-ADNP axis on SOD1G93A mutant motor neuron death induced by trophic factors deprivation. Neuropeptides. https://doi.org/10.1016/j.npep.2023.102386