Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Parkinson's disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson's disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.Junta de Andalucia P18-RT-3324 P20-01293 P20-01061Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2019-110960GB-I0

A western representative of an eastern clade: phylogeographic history of the gypsum-associated plant Nepeta Hispanica

The preference of certain plant species for gypsum soils with a patchy distribution leads to disjunct population structures that are thought to generate island-like dynamics potentially influencing biogeographic patterns at multiple evolutionary scales. Here, we study the evolutionary and biogeographic history of Nepeta hispanica, a western Mediterranean plant associated with gypsum soils and displaying a patchy distribution with populations very distant from each other. Three approaches were used: (a) interspecific phylogenetic analyses based on nuclear DNA sequences of the ITS region to unveil the relationships and times of divergence between N. hispanica and its closest relatives; (b) phylogeographic analyses using plastid DNA regions trnS-trnG and psbJ-petA to evaluate the degree of genetic isolation between populations of N. hispanica, their relationships and their genetic diversity; and (c) ecological niche modelling to evaluate historical distributional changes. Results reveal that N. hispanica belongs to an eastern Mediterranean and Asian (Irano-Turanian) clade diversified in arid environments since the Miocene-Pliocene. This species represents the only lineage of this clade that colonised the western Mediterranean, probably through the northern Mediterranean coast (southern Europe). Present Iberian populations display a high plastid genetic diversity and, even if geographically distant from each other, they are highly connected according to the distribution of plastid haplotypes and lineages. This can be explained by a scenario involving a complex history of back-and-forth colonisation events, facilitated by a relative stability of suitable conditions for the species across the western Mediterranean throughout the QuaternaryThis work would not have been possible without the support of Julian ´ García, Rub´en de Pablo, Jesús del Río, Leonardo Guti´errez, Javier Puente, Javier Pavon ´ and Luis M. Medrano, who helped us with field sample collection; Leopoldo Medina, Cyrille Chatelain, Jesús Riera and Javier Hernandez, ´ who granted us permission to use specimens from the MA, G, VAL and SALA herbaria respectively; and Emilio Cano, who provided his invaluable help in the RJB-CSIC molecular systematics laboratory. Fieldwork was financed by the Universidad Autonoma ´ de Madrid with a grant to IRG’s Master thesis. Laboratory work was funded by a Juan de la Cierva fellowship to MF-M (Spanish Ministry of Economy and Competitiveness, reference IJCI-2015–23459

La discapacidad visual en el municipio de Artemisa

Se realizó un estudio sobre discapacidad en el municipio de Artemisa, en abril del 2003, con vistas a determinar la prevalencia de la minusvalía visual, detectándose la misma en un 30,8%. Dentro de las causas más frecuentes se encontraron el glaucoma con 9,52% y las ametropías con 8,40%. Existió un subregistro de algunas enfermedades invalidantes de la agudeza visual como la retinosis pigmentaria, los cuadros degenerativos y las cataratas por presentar muy escaso porcentaje, siendo las mismas causas de cegueras en el mundo

Poor Cognitive Agility Conservation in Obese Aging People

Life expectancy has been boosted in recent decades at expenses of increasing the ageassociated diseases. Dementia, for its incidence, stands out among the pathologies associated with aging. The exacerbated cognitive deterioration disables people from carrying out their daily lives autonomously and this incidence increases exponentially after 65 years of age. The etiology of dementia is a miscellaneous combination of risk factors that restrain the quality of life of our elderly. In this sense, it has been established that some metabolic pathologies such as obesity and diabetes act as a risk factor for dementia development. In contrast, a high educational level, as well as moderate physical activity, have been shown to be protective factors against cognitive impairment and the development of dementia. In the present study, we have evaluated the metabolic composition of a population between 60–90 years old, mentally healthy and with high academic degrees. After assessing agility in mental state, we have established relationships between their cognitive abilities and their body composition. Our data support that excess body fat is associated with poorer maintenance of cognition, while higher percentages of muscle mass are associated with the best results in the cognitive tests.Junta de Andalucia European Commission P20-01061 P18-RT-3324 P20-01293 PECART-0096-2020Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2019-110960GB-I0

Satisfaction, Assessment and Adaptation to a Virtual Environment of the University Mentoring Programme GuíaMe-AC-UMA for Gifted High School Students

The purpose of this study is to analyse the satisfaction levels of participants (mentees, mentors, and technical-research team) of a university mentoring programme. The GuíaMe-AC-UMA is aimed at gifted high school students. Due to the COVID-19 pandemic, the IX edition was carried out in an online format. The results were compared to those of the in-person edition (VII edition) to assess whether there were differences between the editions. For this purpose, three versions (one for each participant type) of a Likert-type questionnaire were distributed among the participants of the 22 workshops offered by the GuíaMe-AC-UMA Programme. A total of 224 responses were received: 21 from the mentors, 181 from the mentees and 22 from the technical-research team. The results indicate a high level of satisfaction with the development of the workshops by all participants. While the mentees preferred the in-person edition, the rest of the participants showed no difference in satisfaction levels between editions. A similar result was observed when correcting for the subject area of the workshop. The in-person edition was valued higher than the online version by all. The overall level of satisfaction shown by all participants and the support for continuation of the programme suggest that this type of educational offer is beneficial and satisfactory for all involved, in accordance with previous research on mentoring programmes. These results indicate that programmes focused on young pre-university students with high abilities are valued; these results encourage us to continue the programmeThis research received no external funding.Partial funding for open access charge: Universidad de Málag

Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

L.M.-R. and J.J.R.-R. are funded by P20-01293 from Junta de Andalucia, Spain. J.J.R.-R. is additionally funded by PECART-0096-2020 from Junta de Andalucia, Spain and PID2020-117544RB-100 from the Ministry of Science and Innovation, Spain.Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by cognitive decline and progressive memory loss. The aim of this review was to update the state of knowledge on the pathophysiological mechanisms, diagnostic methods and therapeutic approach to AD. Currently, the amyloid cascade hypothesis remains the leading theory in the pathophysiology of AD. This hypothesis states that amyloid-beta (A beta) deposition triggers a chemical cascade of events leading to the development of AD dementia. The antemortem diagnosis of AD is still based on clinical parameters. Diagnostic procedures in AD include fluid-based biomarkers such as those present in cerebrospinal fluid and plasma or diagnostic imaging methods. Currently, the therapeutic armory available focuses on symptom control and is based on four pillars: pharmacological treatment where acetylcholinesterase inhibitors stand out; pharmacological treatment under investigation which includes drugs focused on the control of A beta pathology and tau hyperphosphorylation; treatment focusing on risk factors such as diabetes; or nonpharmacological treatments aimed at preventing development of the disease or treating symptoms through occupational therapy or psychological help. AD remains a largely unknown disease. Further research is needed to identify new biomarkers and therapies that can prevent progression of the pathology.Junta de Andalucia European Commission P20-01293 PECART-0096-2020Spanish Government European Commission PID2020-117544RB-10

Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alphasynuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson’s disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer’s disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.P20-01293 from Junta de Andalucía, SpainP20-01061 from Junta de Andalucía, SpainPID2019-110960GB-I00 from the Ministry of Science and Innovation, Spai

Downregulation of epidermal growth factor receptor in hepatocellular carcinoma facilitates transforming growth factor-β-induced epithelial to amoeboid transition

The Epidermal Growth Factor Receptor (EGFR) and the Transforming Growth Factor-beta (TGF-β) are key regulators of hepatocarcinogenesis. Targeting EGFR was proposed as a promising therapy; however, poor success was obtained in human hepatocellular carcinoma (HCC) clinical trials. Here, we describe how EGFR is frequently downregulated in HCC patients while TGF-β is upregulated. Using 2D/3D cellular models, we show that after EGFR loss, TGF-β is more efficient in its pro-migratory and invasive effects, inducing epithelial to amoeboid transition. EGFR knock-down promotes loss of cell-cell and cell-to-matrix adhesion, favouring TGF-β-induced actomyosin contractility and acquisition of an amoeboid migratory phenotype. Moreover, TGF-β upregulates RHOC and CDC42 after EGFR silencing, promoting Myosin II in amoeboid cells. Importantly, low EGFR combined with high TGFB1 or RHOC/CDC42 levels confer poor patient prognosis. In conclusion, this work reveals a new tumour suppressor function for EGFR counteracting TGF-β-mediated epithelial to amoeboid transitions in HCC, supporting a rational for targeting the TGF-β pathway in patients with low EGFR expression. Our work also highlights the relevance of epithelial to amoeboid transition in human tumours and the need to better target this process in the clinic