Sara Alexandra Matos dos Santos

146 Pages·2014·13.96 MB·Portuguese

Universidade de Lisboa

Faculdade de Medicina de Lisboa

KYOTORPHIN DERIVED PEPTIDES IN THE RELATIONSHIP BETWEEN
ANALGESIA AND ALZHEIMER’S DISEASE

Sara Alexandra Matos dos Santos

Doctorate in Biomedical Sciences

Specialty in Medical Biochemistry

2014
Universidade de Lisboa

Faculdade de Medicina de Lisboa

KYOTORPHIN DERIVED PEPTIDES IN THE RELATIONSHIP BETWEEN
ANALGESIA AND ALZHEIMER’S DISEASE

Sara Alexandra Matos dos Santos
Thesis supervised by Prof. Doctor Miguel Augusto Rico Botas Castanho

Doctorate in Biomedical Sciences
Specialty in Medical Biochemistry

Todas as afirmações efectuadas no presente documento são da exclusiva
responsabilidade do seu autor, não cabendo qualquer responsabilidade à Faculdade de
Medicina de Lisboa pelos conteúdos nele apresentados.

A impressão desta dissertação foi aprovada pelo Conselho Científico da
Faculdade de Medicina de Lisboa em reunião de 22 de Abril de 2014.

Acknowledgments

During my PhD, I contacted and collaborated with many people that, in various ways,
helped me to achieve my goals. I am thankful to all of them for their help and support.
From these persons, I would like to highlight:

Firstly, I am extremely grateful to Professor Miguel Castanho, my supervisor, for letting
me join his group in the Institute of Molecular Medicine and for all the support and
companionship he demonstrated during the development of my thesis. Without him
and his critical and entrepreneurial spirit this work would have never been possible. I
am honored to have worked under his supervision.

The actual and past members of UBqF Unit (IMM, FMUL), for their support and
friendship, and for receiving me so well. Specially to Marta Ribeiro for helping me to
enter into a world far from my clinical day to day activities. To Sónia Sá Santos for all
her help and the long hours working together in the pursuit of our projects. To Antónia
Pinto for all her support and insight in the field of animal experimentation.

The people of the Neurosciences Unit of the IMM for all the support and teaching in
the field of animal behavior.

The people from the Department of Experimental Biology in Oporto, Faculty of
Medicine, formerly Institute of Histology and Embryology, especially Professor Isaura
Tavares for all the collaboration.

The people from the laboratory of metabolopathies of the Clinical Hospital of Santiago
Compostela, especially Professors José Cocho and Laura Garcia-Nimo for all their
willingness in helping with the development of mass spectrometry techniques to
detect biomarkers in biological fluids.

I thank the Instituto de Medicina Molecular and the Faculty of Medicine of the
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University of Lisbon for providing all the facilities to perform my work and all people
from there for the great atmosphere.
I thank all my colleagues and staff who worked with me at the Hospital Prof Dr
Fernando Fonseca, specially the Neurology and Anesthesiology services.
I thank all the patients and their families for their willingness to participate, despite the
difficult situations in which they find themselves. I thank them for keeping hope and
the will to fight.
I thank my friends Violeta and Baltazar for all the support and cherish during my long
hours of work.
Lastly, I want to thank my family for all their support, motivation and comprehension
along this journey.
To my grandmother Amélia, herself another victim of this terrible disease.
To my parents, who always encouraged me to do my very best and to pursue my
dreams.
To Rui, for all his love, support and patience.
And lastly, to the recently arrived baby Alice, an authentic revolution in our lives, for all
the hope and joy she embodies. This thesis is dedicated to her, with all my love.

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Preface

My PhD was devoted to the study of the possible relationship of pain and Alzheimer
disease (AD) using the analgesic Kyotorphin as a bridge.
I became very interested in the area of chronic pain still on the faculty of Medicine.
Later, I started my hospital rotations and this area changed from a theoretical to a
practical subject, since pain is one of the main complaints that drive patients to
hospitals. The study and treatment of chronic pain were some of the reasons why I
chose the residency in Anesthesiology.
I always found laboratory work and basic research fascinating, so the possibility of
working at the Institute of Molecular Medicine - Faculty of Medicine was a great
opportunity to develop my PhD and link basic and clinical research.
I was fortunate enough to know Professor Miguel Castanho and his group, who
proposed me a translational project involving the study of the peptide kyotorphin in
the relation between pain and neurodegeneration.
This project conducted to pain evaluation in patients with the diagnosis of Alzheimer
disease using validated scales. Later, the quantification of kyotorphin in the cerebro-
spinal fluid of AD patients was determined. To achieve this, we collaborated with the
laboratory of metabolopathies of the Hospital of Santiago Compostela, with the
development of mass spectrometry techniques to detect KTP in biological fluids. The
results were promising enough to advance further to the testing of kyotorphin derived
peptides in an animal model of Alzheimer disease.
During this path I worked with people specialized in the various fields the work
involved, namely pain, neurosciences and biochemistry, which was a very enriching
experience.

My PhD work originated the following papers, most of them already published:

I. Biomedical applications of di- and tri-peptides
Santos SM, Torcato I, Castanho M
Biopolymeres Peptide Science (2012) Volume 98, Issue 4, pages 288–293 (DOI:
10.1002/bip.22067)
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