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α-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y.
Nascimento, Ana Carolina; Erustes, Adolfo G; Reckziegel, Patrícia; Bincoletto, Claudia; Ureshino, Rodrigo P; Pereira, Gustavo J S; Smaili, Soraya S.
Afiliación
  • Nascimento AC; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil.
  • Erustes AG; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil.
  • Reckziegel P; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil.
  • Bincoletto C; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil.
  • Ureshino RP; Department of Biological Sciences, Diadema Campus, Universidade Federal de São Paulo (UNIFESP), Professor Arthur Riedel Street, Diadema, SP, 09972-270, Brazil.
  • Pereira GJS; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil. gustavo.pereira@unifesp.br.
  • Smaili SS; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio Street, 100, São Paulo, SP, 04044-020, Brazil. ssmaili@unifesp.br.
Neurochem Res ; 45(11): 2749-2761, 2020 Nov.
Article en En | MEDLINE | ID: mdl-32915398
Although the etiology of Parkinson's disease (PD) is multifactorial, it has been linked to abnormal accumulation of α-synuclein (α-syn) in dopaminergic neurons, which could lead to dysfunctions on intracellular organelles, with potential neurodegeneration. Patients with familial early-onset PD frequently present mutation in the α-syn gene (SNCA), which encodes mutant α-syn forms, such as A30P and A53T, which potentially regulate Ca2+ unbalance. Here we investigated the effects of overexpression of wild-type α-syn (WT) and the mutant forms A30P and A53T, on modulation of lysosomal Ca2+ stores and further autophagy activation. We found that in α-syn-overexpressing cells, there was a decrease in Ca2+ released from endoplasmic reticulum (ER) which is related to the increase in lysosomal Ca2+ release, coupled to lysosomal pH alkalization. Interestingly, α-syn-overexpressing cells showed lower LAMP1 levels, and a disruption of lysosomal morphology and distribution, affecting autophagy. Interestingly, all these effects were more evident with A53T mutant isoform when compared to A30P and WT α-syn types, indicating that the pathogenic phenotype for PD is potentially related to impairment of α-syn degradation. Taken together, these events directly impact PD-related dysfunctions, being considered possible molecular targets for neuroprotection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Alfa-Sinucleína / Lisosomas Límite: Humans Idioma: En Revista: Neurochem Res Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Alfa-Sinucleína / Lisosomas Límite: Humans Idioma: En Revista: Neurochem Res Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos