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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

alpha-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y

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Nascimento, Ana Carolina [1] ; Erustes, Adolfo G. [1] ; Reckziegel, Patricia [1] ; Bincoletto, Claudia [1] ; Ureshino, Rodrigo P. [2] ; Pereira, Gustavo J. S. [1] ; Smaili, Soraya S. [1]
Total Authors: 7
[1] Univ Fed Sao Paulo UNIFESP, Dept Pharmacol, Escola Paulista Med, Rua Tres Maio St 100, BR-04044020 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo UNIFESP, Dept Biol Sci, Diadema Campus, Prof Arthur Riedel St, BR-09972270 Diadema, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Neurochemical Research; SEP 2020.
Web of Science Citations: 0

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)

FAPESP's process: 19/02821-8 - Autophagy modulation by cannabinoids: neuroprotection in Parkinson's Disease
Grantee:Soraya Soubhi Smaili
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/20796-2 - Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models
Grantee:Rodrigo Portes Ureshino
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/20073-2 - Autophagy as a protective mechanism in senescent rats
Grantee:Soraya Soubhi Smaili
Support type: Regular Research Grants
FAPESP's process: 17/10863-7 - Study of lipophagy mediated by two-pore channels receptors
Grantee:Gustavo José da Silva Pereira
Support type: Regular Research Grants