Neuroprotective effects of violacein in a model of inherited amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacei...

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Detalhes bibliográficos
Autores: Olivares-Bravo, Silvia, Bolatto, Carmen, Otero Damianovich, Gabriel, Stancov, Matías, Cerri, Sofía, Rodríguez, Paola, Boragno, Daniela, Hernández Mir, Karina, Cuitiño, María Noel, Larrambembere, Fernanda, Isasi, Eugenia, Alem, Diego, Canclini, Lucía, Marco, Marta, Davyt, Danilo, Díaz-Amarilla, Pablo
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:Uruguay
Recursos:Universidad de la República
Repositório:COLIBRI
Idioma:inglês
OAI Identifier:oai:colibri.udelar.edu.uy:20.500.12008/54513
Acesso em linha:https://hdl.handle.net/20.500.12008/54513
Access Level:Acceso aberto
Palavra-chave:ESCLEROSIS AMIOTRÓFICA LATERAL
ADMINISTRACIÓN DEL TRATAMIENTO FARMACOLÓGICO
GENÉTICA
ANIMALES
MODELOS ANIMALES DE ENFERMEDAD
INDOLES
METALOPROTEINASA 2 DE LA MATRIZ
RATONES TRANSGÉNICOS
NEURONAS MOTORAS
PATOLOGÍA CLÍNICA
FARMACOLOGÍA
ENFERMEDADES NEURODEGENERATIVAS
RATAS
FÁRMACOS NEUROPROTECTORES
USOS TERAPÉUTICOS
MÉDULA ESPINAL
Descrição
Resumo:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacein with several reported protective/antiproliferative properties may control highly neurotoxic astrocytes (AbAs) obtained from spinal cord cultures of symptomatic hSOD1G93A rats, and if it could be neuroprotective in this ALS experimental model. At concentrations lower than those reported as protective, violacein selectively killed aberrant astrocytes. Treatment of hSOD1G93A rats with doses equivalent to the concentrations that killed AbAs caused a marginally significant delay in survival, partially preserved the body weight and soleus muscle mass and improved the integrity of the neuromuscular junction. Reduced motor neuron death and glial reactivity was also found and likely related to decreased inflammation and matrix metalloproteinase-2 and -9. Thus, in spite that new experimental designs aimed at extending the lifespan of hSOD1G93A rats are needed, improvements observed upon violacein treatment suggest a significant therapeutic potential that deserves further studies.

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