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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.)

Restoration of Rab1 Levels Prevents Endoplasmic Reticulum Stress in Hippocampal Cells during Protein Aggregation Triggered by Rotenone

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Lima, Nathan C. R. [1] ; Melo, Thaiany Q. [1] ; Sakugawa, Andressa Y. S. [1] ; Melo, Karla P. [1] ; Ferrari, Merari F. R. [1]
Total Authors: 5
[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao, 277, Cidade Univ, BR-05508090 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Neuroscience; v. 419, p. 5-13, NOV 1 2019.
Web of Science Citations: 0

Disrupted neuronal intracellular trafficking is often related with protein aggregates present in the brain during neurodegenerative diseases such as Alzheimer's. Impairment of intracellular transport may be related to Rab proteins, a class of small GTPases responsible for trafficking of organelles and vesicles. Deficit in trafficking between the endoplasmic reticulum (ER) and Golgi apparatus mediated by Rab1 and 6 may lead to increased unfolded protein response (UPR) and ER stress and remodeling. Thus, the objective of this study is to analyze the levels of Rabs 1 and 6 in the hippocampus of aged rats and in vitro during protein aggregation promoted by exposure to rotenone. Levels of Rabs 1 and 6, ATF6 and CHOP were measured by western blotting. PDI immunolabeling and ER-Tracker were employed to study ER morphology. MTT was used to analyze cell metabolism. Rab1 levels and cell viability decreased, whereas Rab6, UPR proteins and ER remodeling increased during protein aggregation, which were restored to normal levels after exogenous expression of Rab1.These results suggest that decrease of Rab1 levels contributes to ER stress and remodeling, while maintaining the elevated expression of Rab1 prevented impairment of cell viability during protein aggregation. In conclusion, Rab1 is a significant player to maintain intracellular homeostasis and its expression may mitigate ER dysfunction in the context of neurodegeneration-related protein inclusions. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 17/14273-0 - Analysis of mitophagy in a cellular model of protein aggregation associated with neurodegeneration
Grantee:Karla Pacheco de Melo
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/10892-1 - Study of the inflammatory mechanisms mediated by innate immunity receptors in Amyotrophic Lateral Sclerosis
Grantee:Renato Barboza
Support Opportunities: Regular Research Grants
FAPESP's process: 11/06434-7 - Degradation of hyperphosphorylated tau and organelles trafficking during neurodegenerative processes linked to protein aggregation in hypoccampal cell cultures
Grantee:Merari de Fátima Ramires Ferrari
Support Opportunities: Regular Research Grants
FAPESP's process: 15/18961-2 - Study of autophagy as the driving mechanism of neurodegenerative diseases
Grantee:Merari de Fátima Ramires Ferrari
Support Opportunities: Regular Research Grants