Paula I Moreira

Paula I Moreira
University of Coimbra | UC · Faculty of Medicine

PhD
Assistant Professor-Faculty of Medicine, Principal Investigator-Center for Neuroscience and Cell Biology, Univ. Coimbra

About

336
Publications
144,674
Reads
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26,166
Citations
Introduction
Our research group aims to elucidate the role of mitochondria-linked mechanisms, hypoxic stress signaling and sex dimorphism in brain changes associated to diabetes and age-related neurodegenerative diseases, particularly Alzheimer disease. We are also interested in studying the preventive and/or therapeutic potential of some pharmacological and non-pharmacological strategies. To achieve our goals, we use several experimental models such as human samples and in vitro and in vivo/ex vivo models.
Additional affiliations
January 2016 - present
University of Coimbra
Position
  • Professor (Assistant)
December 2011 - December 2016
University of Coimbra
Position
  • Professor (Assistant)
September 2007 - present
University of Coimbra
Position
  • Principal Investigator
Description
  • Alzheimer's disease, Diabetes, Metabolic hormones, Metabolism
Education
April 2005 - September 2005
Case Western Reserve University
Field of study
  • Neuroscience - Mitochondria involvement in Alzheimer's disease
January 2003 - July 2017
University of Coimbra
Field of study
  • Neuroscience

Publications

Publications (336)
Article
Full-text available
The retina, as part of the central nervous system (CNS), can be the perfect target for in vivo, in situ, and noninvasive neuropathology diagnosis and assessment of therapeutic efficacy. It has long been established that several age-related brain changes are more pronounced in Alzheimer's disease (AD). Nevertheless, in the retina such link is still...
Article
Full-text available
Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activatio...
Article
Aims: Brief episodes of sublethal hypoxia reprogram brain response to face possible subsequent lethal stimuli by triggering adaptive and pro-survival events - a phenomenon denominated hypoxic preconditioning (HP). To date, the potential therapeutic implications of HP to forestall sporadic Alzheimer's disease (sAD) pathology remain unexplored. Usin...
Article
Full-text available
Oxygen sensing and homeostasis is indispensable for the maintenance of brain structural and functional integrity. Under low-oxygen tension, the non-diseased brain has the ability to cope with hypoxia by triggering a homeostatic response governed by the highly conserved hypoxia-inducible family (HIF) of transcription factors. With the advent of adva...
Chapter
The increase in life expectancy is one of the highest accomplishments of humankind. Yet, this situation is also one of the most challenging public health issues. Despite the inevitable advancement of biological age, the deterioration of physiological homeostasis is variable and a better knowledge of the molecular mechanisms behind the complexity of...
Article
Full-text available
Diabetes is a chronic metabolic disease that seriously compromises human well-being. Various studies highlight the importance of maintaining a sufficient glucose supply to the brain and subsequently safeguarding cerebral glucose metabolism. The goal of the present work is to clarify and disclose the metabolic alterations induced by recurrent hypogl...
Article
Full-text available
Alzheimer’s disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-β (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events...
Article
Full-text available
The concept 'the retina as a window to the brain' has been increasingly explored in Alzheimer´s disease (AD) in recent years, since some patients present visual alterations before the first symptoms of dementia. The retina is an extension of the brain and can be assessed by noninvasive methods. However, assessing the retina for AD diagnosis is stil...
Article
Full-text available
Mice are widely used as models for many diseases, including eye and neurodegenerative diseases. However, there is a lack of normative data for retinal thickness over time, especially at young ages. In this work, we present a normative thickness database from one to four-months-old, for nine layers/layer-aggregates, including the total retinal thick...
Article
Full-text available
Background: T2D is a global epidemic, and a major risk factor for cognitive decline and dementia. Thus, it is of utmost importance to elucidate the mechanisms underlying T2D- associated neurodegeneration. WWOX is known to participate in several molecular interactions, signaling and apoptosis. However, the possible involvement of WWOX in T2D brain c...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Insulin-like growth factor 1 receptor (IGF1R)-mediated signaling pathways modulate important neurophysiological aspects in the central nervous system, including neurogenesis, synaptic plasticity and complex cognitive functions. In the present study, we intended to characterize the impact of IGF1R deficiency in the brain, focusing on PI3K/Akt and MA...
Article
Full-text available
The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the prese...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Chapter
Alzheimer’s disease (AD), the most common form of dementia, affects 55 million people worldwide, and this number is expected to increase to 88 million by 2050. Understanding the molecular mechanisms underpinning pathological cognitive deficits and AD onset and progression is urgently needed, to identify biomarkers and therapeutic targets. Besides a...
Article
Full-text available
Mutations in the PTEN-induced kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (PARKIN) genes are associated with familial forms of Parkinson's disease (PD). PINK1, a protein kinase, and PARKIN, an E3 ubiquitin ligase, control the specific elimination of dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial network an...
Article
Full-text available
Trace elements (TE) homeostasis is crucial in normal brain functioning. Although imbalances have the potential to exacerbate events leading neurodegenerative diseases, few studies have directly addressed the eventual relationships between TE levels in the human body and future cognitive status. The present study aimed to assess how different TE bod...
Chapter
Medical and scientific communities have been striving to disentangle the complexity of neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), in order to develop a cure or effective treatment for these diseases. Along this journey, it has become important to identify the early events occurring in the prodrom...
Article
Full-text available
The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become impor...
Article
Full-text available
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder whose diagnosis remains a notable challenge. The literature suggests that cerebral changes precede AD symptoms by over two decades, implying a significantly advanced stage of AD by the time it is usually diagnosed. In the study herein, texture analysis was applied to computed opti...
Article
Full-text available
The treatment options for a patient diagnosed with Alzheimer’s disease (AD) are currently limited. The cerebral accumulation of amyloid-β (Aβ) is a critical molecular event in the pathogenesis of AD. When the amyloidogenic β-secretase (BACE1) is inhibited, the production of Aβ peptide is reduced. Henceforth, the main goal of this study is the disco...
Chapter
Full-text available
Alzheimer’s disease (AD) is an intriguing and still unsolved puzzle that has attracted, over the last decades, the interest of the scientific community. Despite the limited knowledge regarding the initial cause(s) of AD, mitochondrial abnormalities have been pinpointed as one of the earliest and strongest events related with the pathological course...
Article
Full-text available
Alzheimer’s disease (AD) is the most common form of dementia worldwide, being characterized by the deposition of senile plaques, neurofibrillary tangles (enriched in the amyloid beta (Aβ) peptide and hyperphosphorylated tau (p-tau), respectively) and memory loss. Aging, type 2 diabetes (T2D) and female sex (especially after menopause) are risk fact...
Preprint
Full-text available
Background: The concept 'the retina as a window to the brain' in Alzheimer´s disease (AD) has been explored in recent years since patients sometimes present visual alterations before the first symptoms of dementia. The retina is an extension of the brain and can be assessed by non-invasive methods. However, assessing the retina for AD diagnosis is...
Article
Mood disorders like major depression and bipolar disorder (BD) are among the most prevalent forms of mental illness. Current knowledge of the neurobiology and pathophysiology of these disorders is still modest and clear biological markers are still missing. Thus, a better understanding of the underlying pathophysiological mechanisms to identify pot...
Article
A diverse range of N-terminally truncated and modified forms of amyloid-β (Aβ) oligomers have been discovered in Alzheimer’s disease brains, including the pyroglutamate-Aβ (AβpE3). AβpE3 species are shown to be more neurotoxic when compared with the full-length Aβ peptide. Findings visibly suggest that glutaminyl cyclase (QC) catalyzed the generati...
Article
Full-text available
Purpose In this work, we aimed to assess the difference in thickness of the retina of the triple‐transgenic mice model of Alzheimer’s disease (3xTg‐AD), compared to controls (wild‐type ‐ WT), at the age of one month. Methods Mice’s retinas were imaged by optical coherence tomography (OCT) using the Phoenix Micron IV OCT (Phoenix Research Labs, USA...
Poster
Full-text available
Degenerative brain diseases that perturb progressive and irreversibly brain function, including memory, cognitive and behavioral skills, are devastating the lives of millions of people. Currently, 45 million of people worldwide suffers from Alzheimer's disease (AD) without any reliable tool to stop or even slow its progression. However, it is well...
Article
Full-text available
In the present study, trace elements (TE) levels were evaluated in scalp hair along the continuum from healthy subjects (HS) to patients suffering from subjective memory concerns (SMC), and/or mild cognitive impairment (MCI), and those with already installed dementia (DEM) in order to: (i) assess the effects of environmental and lifestyle factors o...
Article
Full-text available
Background: It has been claimed that the retina can be used as a window to study brain disorders. However, concerning Alzheimer's disease (AD), it still remains controversial whether changes occurring in the brain and retina are associated. We aim to understand when changes start appearing in the retina and brain, how changes progress, and if they...
Article
Full-text available
Abnormal protein homeostasis (proteostasis), dysfunctional mitochondria, and aberrant redox signalling are often associated in neurodegenerative disorders, such as Huntington's (HD), Alzheimer's and Parkinson's diseases. It remains incompletely understood, however, how changes in redox signalling affect proteostasis mechanisms, including protein de...
Article
Full-text available
The aim of this study was to identify links between potential long-term environmental exposure to mixed contamination and the neuropsychological performance of a group of adults (> 55 years old) living near an industrial facility. Fifty-eight permanent residents were evaluated with the Mini-Mental State Examination and Clinical Dementia Rating scal...
Conference Paper
In this work, we imaged the retina of wild-type and triple-transgenic mice model of Alzheimer’s disease (AD) (3xTg-AD), at the ages of one and two months, by optical coherence tomography. Texture analysis of calculated fundus images, for the six most anterior layers of the retina, present widespread differences between groups, demonstrating that re...
Article
Alzheimer's disease (AD) is the most common form of dementia in the elderly and, despite the tremendous efforts researchers have put into AD research, there are no effective options for prevention and treatment of the disease. The best way to reach this goal is to clarify the mechanisms involved in the onset and progression of AD. In the last few y...
Article
Full-text available
Alzheimer’s disease is the most frequent cause of dementia worldwide, representing a global health challenge, with a massive impact on the quality of life of Alzheimer’s disease patients and their relatives. The diagnosis of Alzheimer’s disease constitutes a real challenge, because the symptoms manifest years after the first degenerative changes oc...
Conference Paper
Full-text available
The development of effective medicines to break or delay the progressive brain degeneration underlying Alzheimer’s disease (AD) is one greatest challenge of our time. In the present work, a selected pool of white wine polyphenols, designed as PVPP-withe wine extract, was characterized and used to prepare a polyphenols-enriched diet, supplementing t...
Chapter
Due to the exponential growth of aging population worldwide, neurodegenerative diseases became a major public health concern. Among them, Alzheimer’s disease (AD) prevails as the most common in the elderly, rendering it a research priority. After several decades considering the brain as an insulin-insensitive organ, recent advances proved a central...
Article
Full-text available
Post-translational modifications (PTMs) such as phosphorylation, glycosylation, methylation, acetylation, ubiquitination, nitrosylation, SUMOylation and many other types, are crucial regulators of protein properties and functions1. PTMs can modulate the turnover, localization, activity, and interaction of proteins thus, playing a crucial role in th...
Article
Full-text available
The understanding of the natural history of Alzheimer's disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and...
Chapter
In developed and developing countries, the adoption of high calorie diets and a sedentary lifestyle have been major contributors in the inflating number of obese and/or type 2 diabetic (T2D) individuals. In spite of the strong will to promote and increase the awareness of the importance of an active healthy life and aging, the current obesity and T...
Article
Uncover the initial cause(s) underlying Alzheimer's disease (AD) pathology is imperative for the development of new therapeutic interventions to counteract AD-related symptomatology and neuropathology in a timely manner. The early stages of AD are characterized by a brain hypometabolic state as denoted by faulty glucose uptake and utilization and a...
Article
Full-text available
New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson’s, Alzheimer’s and sclerosis’ diseases. This study proposes a multi-disciplinary approach combining neurosci...
Article
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The last decades have been marked by an increased prevalence in non-communicable diseases such as obesity and type 2 diabetes (T2D) as well as by population aging and age-related (brain) diseases. The current notion that the brain and the body are interrelated units is gaining the attention of the scientific and medical community. Growing evidence...
Conference Paper
Background Huntington’s disease (HD) is characterized by cortico-striatal neuronal loss, energy dysmetabolism and type 2 diabetes (T2D) features. Thus, an efficient anti-T2D drug like liraglutide may protect against HD. Albeit the HD-related cachexia and liraglutide’s anorectic features, its peripheral (co-) administration with the orexigenic ghrel...
Conference Paper
Background Huntington’s disease (HD) is caused by mutant huntingtin (mHtt) and presents increased oxidative stress biomarkers, suggesting that aberrant redox signaling is associated with HD pathogenesis. Treatment with MitoQ, a mitochondria-targeted antioxidant, was neuroprotective in other models of neurodegenerative disorders, including ALS, Park...
Article
Full-text available
The brain is one of the most exquisite organs in the body with high metabolic demands, and requires a tight regulation of the surrounding environment. This tight control is exerted by the neurovascular unit (NVU) comprising different cell types, where endothelial cells play the commander-in-chief role. Thus, it is assumable that even slight perturb...
Article
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Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Co...
Article
Full-text available
Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common type of dementia in the elderly. The clinical symptoms of AD include a progressive loss of memory and impairment of cognitive functions interfering with daily life activities. The main neuropathological features consist in extracellular amyloid-β (Aβ) plaque deposit...
Article
Full-text available
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin...
Article
Since the first clinical case reported more than 100 years ago, it has been a long and winding road to demystify the initial pathological events underling the onset of Alzheimer's disease (AD). Fortunately, advanced imaging techniques extended the knowledge regarding AD origin, being well accepted that a decline in brain glucose metabolism occurs d...
Article
Full-text available
A growing body of evidence supports a clear association between Alzheimer's disease and diabetes and several mechanistic links have been revealed. This paper is mainly devoted to the discussion of the role of diabetes-associated mitochondrial defects in the pathogenesis of Alzheimer's disease. The research experience and views of the author on this...
Article
Doxorubicin (DOX) is a widely used antineoplastic agent for a wide range of cancers, including hematological malignancies, soft tissue sarcomas and solid tumors. However, DOX exhibits a dose-related toxicity that results in life-threatening cardiomyopathy. In addition to the heart, there is evidence that DOX toxicity extends to other organs. This g...
Article
Full-text available
Though glucose fluctuations have been considered as an adverse factor for the development of several diabetes-related complications, their impact in the central nervous system is still not fully elucidated. This study was conducted to evaluate the responses of neuronal cells to different glycemic exposures alongside to elucidate the role of uncoupl...
Article
Alzheimer's disease (AD) constitutes a major socioeconomic challenge due to its disabling features and the rise in prevalence (especially among (peri)menopausal women and type 2 diabetes patients). The precise etiopathogenesis of AD remains poorly understood. Importantly, its neurodegenerative perspective has been challenged towards a more “systemi...
Article
Full-text available
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and incre...
Chapter
Full-text available
It is widely accepted that high calorie diets and a sedentary lifestyle sturdily influence the incidence and outcome of type 2 diabetes and obesity, which can occur simultaneously, a situation called diabesity. Tightly linked with metabolic and energy regulation, a close association between diabetes and Alzheimer’s disease (AD) has been propose