| Texto completo | |
| Autor(es): |
Nascimento, Ana Carolina
;
Erustes, Adolfo G.
;
Reckziegel, Patricia
;
Bincoletto, Claudia
;
Ureshino, Rodrigo P.
;
Pereira, Gustavo J. S.
;
Smaili, Soraya S.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Neurochemical Research; v. 45, n. 11, p. 13-pg., 2020-09-11. |
| Resumo | |
Although the etiology of Parkinson's disease (PD) is multifactorial, it has been linked to abnormal accumulation of alpha-synuclein (alpha-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 alpha-syn gene (SNCA), which encodes mutant alpha-syn forms, such as A30P and A53T, which potentially regulate Ca(2+)unbalance. Here we investigated the effects of overexpression of wild-type alpha-syn (WT) and the mutant forms A30P and A53T, on modulation of lysosomal Ca(2+)stores and further autophagy activation. We found that in alpha-syn-overexpressing cells, there was a decrease in Ca(2+)released from endoplasmic reticulum (ER) which is related to the increase in lysosomal Ca(2+)release, coupled to lysosomal pH alkalization. Interestingly, alpha-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 alpha-syn types, indicating that the pathogenic phenotype for PD is potentially related to impairment of alpha-syn degradation. Taken together, these events directly impact PD-related dysfunctions, being considered possible molecular targets for neuroprotection. (AU) | |
| Processo FAPESP: | 13/20073-2 - Estudo da autofagia no processo de proteção celular de ratas senescentes |
| Beneficiário: | Soraya Soubhi Smaili |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/02821-8 - Modulação da autofagia por canabinóides: neuroproteção na Doença de Parkinson |
| Beneficiário: | Soraya Soubhi Smaili |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/10863-7 - Estudo da lipofagia mediada pelos receptores two-pore channels |
| Beneficiário: | Gustavo José da Silva Pereira |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 16/20796-2 - Estudo da autofagia mediada pelos receptores de estrógeno para combater a toxicidade da proteína tau em modelos celular e animal de zebrafish |
| Beneficiário: | Rodrigo Portes Ureshino |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |