Endoplasmic reticulum (ER) stress response and ER-mitochondria axis

The major focus of our research is to clarify the biological basis of impaired cellular resilience in brain disorders, namely AD and Bipolar disorder, to identify novel targets for therapeutic intervention and to develop new biomarkers for early diagnosis. More specifically, we aim to elucidate how the disturbance of the Endoplasmic Reticulum (ER) stress response and of the ER-mitochondria axis at the Mitochondria-Associated Membranes (MAMs) can trigger pathological events associated with neuropsychiatric diseases leading to cell damage. We also intend to obtain experimental evidences supporting the therapeutic potential of compounds obtained from Portuguese natural resources.
We use a combination of biochemical and biology cellular and molecular and of in vivo, in vitro and ex vivo models such as genetic animal models, primary cultures of dissociated neurons, cell lines (neuronal, glial, brain endothelial, monocytic), and cells obtained from patients (e.g. monocytes, lymphocytes, fibroblasts).

Cláudia MF Pereira   Principal Investigator		Rosa Resende PhD Researcher		Ana Catarina Pereira MSc Research Fellow (Collab. with MT Cruz)		Marta Pereira   MSc Student (Collab. with MT Cruz)

Fábio Sousa MSc Research Fellow (Coll. with MT Cruz & A Santos)		Patricia Moreira MSc PhD Student (Collab. with  MT Cruz)		Jessica De Pascale   MSc Student		Tânia Fernandes MSc Research Fellow (Coll. with P Moreira)

Alumni

Colaborations

National

A Santos, C Cavadas, L Pereira de Almeida, MT Cruz, P Gomes, P Moreira, SM Cardoso
CNC, University of Coimbra, Portugal  

I Santana & I Baldeiras
Neurology Department, Coimbra University’s Hospitals (CHUC), Portugal  

N Madeira, S Morais, V Santos, A Macedo
Psychiatry Department, Coimbra University’s Hospitals (CHUC), Portugal  

A Carmo, Fernando Rodrigues
Clinical Pathology Department, Coimbra University’s Hospitals (CHUC), Portugal   

Rosário Domingues
Chemistry Department & QOPNA, University of Aveiro, Portugal

Henrique Girão
iCBR & Faculty of Medicine, University of Coimbra, Portugal

Joana Barbosa de Melo
Citogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Portugal

Artur Figueirinha, Lígia Salgueiro, Teresa Batista
Faculty of Pharmacy, University of Coimbra, Portugal

Ana Palmeira, Rita Palmeira
Labfit & University Beira Interior, Covilhã, Portugal
 

International

Paola Pizzo
Department of Biomedical Sciences, University of Padova, Padova, Italy

Carlos Villalobos, Carmen García-Rodríguez
Institute of Molecular Biology and Genetics (IBGM), University of Valladolid, Spain

Ongoing Projects

“The ups and downs of cellular stress: the “MAM hypothesis” for Bipolar disorder pathophysiology” (2018-2021) CENTRO-01-0145-FEDER-028214 (Principal Investigator)

“Skin allergens: molecules with an improbable therapeutic application for Alzheimer’s disease” (2018-2021) CENTRO-01-0145-FEDER-029369 (Role: Co-Principal Investigator)

“InPaCTus” (2018-2021) COMPETE2020 nº 21874 (Role: Principal Investigator sub-project “Extracts of high added value from forest biomass”) “HealthyAging2020” (2017-2020) CENTRO-01-0145-FEDER-000012 (team member)

"New BACE1 inhibitors for the treatment of Alzheimer's disease: an approach for the development of effective and safe substrate-selective inhibitors" (2017-2018) Edgar Cruz e Silva grant, Grupo de Estudos de Envelhecimento Cerebral e Demência, support from Santa Casa da Misericórdia de Lisboa (team member)

“Valorization of the Thermal resorts of the Centre Region - Characterization of the bioactive potential of the thermal water resources of the Region - study of the therapeutic properties of thermal waters - dermocosmetic" (2017-2018) CENTRO-04-3928-FEDER-000010 (team member)

 “Drugs2CAD” (2016-2019), PT2020 nº 003269, SI I&DT (team member)

Selected Publications

Plácido AI, Pereira CF, Correira SC, Carvalho C, Oliveira CR, Moreira PI. (2017) Phosphatase 2A inhibition affects endoplasmic reticulum and mitochondria homeostasis via cytoskeletal alterations in brain endothelial cells. Mol. Neurobiol. 54, 154-168

Ferreira IL, Ferreiro E, Schmidt J, Cardoso JM, Pereira CM, Carvalho AL, Oliveira CR, Rego AC. (2015) Aβ and NMDAR activation cause mitochondrial dysfunction involving ER calcium release. Neurobiol. Aging. 36, 80-92

Fonseca AC, Ferreiro E, Oliveira CR, Cardoso SM, Pereira CF. (2013) Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells. Biochim. Biophys. Acta 1832, 2191-2203

Costa RO, Lacor PN, Ferreira IL, Resende R, Auberson YP, Klein WL, Oliveira CR, Rego AC, Pereira CF. (2012) Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-D-aspartate receptor in mature hippocampal cultures treated with amyloid-β oligomers. Aging Cell 11, 823-833.

Costa RO, Ferreiro E, Martins I, Santana I, Cardoso SM, Oliveira CR, Pereira CM. (2012) Amyloid β-induced ER stress is enhanced under mitochondrial dysfunction conditions. Neurobiol Aging 33, 824.e5-824.e16.

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Reviews

Pereira AC, Resende R, Morais S, Madeira N, Pereira CF. (2017) The ups and downs of cellular stress: the “MAM hypothesis” for Bipolar disorder pathophysiology. Int J Clin Neurosci Mental Health 4 (suppl 3):S04 (open access)

Fonseca AC, Cardoso SM, Pereira CF. (2015) Calcium and redox homeostasis in Alzheimer's disease: a focus on the endoplasmic reticulum. Ther Targets Neurol Dis. 2015, 2: e428 (open access)

Plácido AI, Pereira CM, Duarte AI, Candeias E, Correia SC, Santos RX, Carvalho C, Cardoso S, Oliveira CR, Moreira PI. (2014) The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: Implications for Alzheimer's disease. Biochim Biophys Acta 1842, 1444-1453