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1.
Brain Sci ; 11(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34679356

RESUMO

During the COVID-19 pandemic and the related lockdowns, outpatient follow-up visits for patients with chronic neurological diseases have been suspended. Managing people affected by amyotrophic lateral sclerosis (ALS) has become highly complicated, leaving patients without the standard multidisciplinary follow-up. This study aimed to analyze the impact of the COVID-19 lockdown on ALS disease progression. We compared the clinical data and progression in the first year following diagnosis for patients who received ALS diagnosis during 2020 (G20, N = 34), comparing it with a group of diagnosed in 2018 (G18, N = 31). Both groups received a comparable multidisciplinary model of care in our Tertiary Expert ALS Centre, Novara, Italy. The monthly rate of ALSFRS-R decline during the lockdown was significantly increased in G20 compared to G18 (1.52 ± 2.69 vs. 0.76 ± 0.56; p-value: 0.005). In G20, 47% required non-invasive ventilation (vs. 32% of G18). Similarly, in G20, 35% of patients died vs. 19% of patients in G18 (p-value: 0.01). All results were corrected for gender, age, site of onset, and diagnostic delay. Several factors can be implicated in making ALS more severe, with a faster progression, such as reduced medical evaluations and the possibility of therapeutic changes, social isolation, and rehabilitation therapy suspension.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34355622

RESUMO

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients' mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ≤12 months; (2) ≤18 months; (3) ≤24 months; (4) ≤36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p < 0.001). Median survival decreased when lowering FVC and disease duration cutoffs (p < 0.001); a higher median disease progression rate of included patients led to lower median survival from recruitment. The proportion of recruited fast progressors raised when shortening disease duration and lowering FVC cutoff. Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials' primary endpoints and duration.

4.
Front Neurol ; 12: 637939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393966

RESUMO

Background/objectives: Amyotrophic lateral sclerosis (ALS) is a devastating and still untreatable motor neuron disease. The causes of ALS are unknown, but nutritional factors may impact the rate of disease progression. We aimed to ascertain the influence of coffee and tea consumption on ALS progression rate. Subjects/methods: In this multicenter cross-sectional study, we recruited 241 patients, 96 females, and 145 males; the mean age at onset was 59.9 ± 11.8 years. According to El Escorial criteria, 74 were definite ALS, 77 probable, 55 possible, and 35 suspected; 187 patients had spinal onset and 54 bulbar. Patients were categorized into three groups, according to their ΔFS (derived from ALS Functional Rating Scale-Revised score and disease duration from onset): slow (81), intermediate (80), and fast progressors (80). Results: Current coffee consumers were 179 (74.3%), 34 (14.1%) were non-consumers, and 22 (9.1%) were former consumers, whereas six (2.5%) consumed decaffeinated coffee only. The log-ΔFS was weakly correlated with the duration of coffee consumption (p = 0.034), but not with the number of cup-years, or the intensity of coffee consumption (cups/day). Current tea consumers were 101 (41.9%), 6 (2.5%) were former consumers, and 134 (55.6%) were non-consumers. Among current and former consumers, 27 (25.2%) consumed only green tea, 51 (47.7%) only black tea, and 29 (27.1%) both. The log-ΔFS was weakly correlated only with the consumption duration of black tea (p = 0.028) but not with the number of cup-years. Conclusions: Our study does not support the hypothesis that coffee or tea consumption is associated with the ALS progression rate.

5.
Neurosci Biobehav Rev ; 127: 958-978, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153344

RESUMO

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in animal models and people. We also explore the potential of Positron Emission Tomography to detect neuroinflammation in vivo, and discuss ongoing clinical trials of therapies targeting the immune system. With validation in human patients, new evidence in this emerging field will serve to identify novel therapeutic targets and provide realistic hope for personalized treatment strategies.


Assuntos
Esclerose Amiotrófica Lateral , Doenças Neurodegenerativas , Animais , Humanos , Sistema Imunitário , Tomografia por Emissão de Pósitrons
6.
Artigo em Inglês | MEDLINE | ID: mdl-34151660

RESUMO

Objective: To assess amyotrophic lateral sclerosis (ALS) prevalence and to analyze how this estimate vary according to the historical depth of data collection. Methods: Data from the PARALS register have been used. Crude prevalence ratio was estimated on 31 December 2015 for the period 2015-2013 and then repeated extending the time interval by 3 years each time. For each time interval, prevalence ratio was calculated globally and stratified by sex, age at diagnosis, and phenotype. Prevalence was also calculated considering patients who underwent tracheostomy during the same study period. Results: Prevalence ratios increased proportionally to the length of the time period considered, ranging from 6 (95% CI 5.3-6.7) for a 3-year period to 12.1 (95% CI 11.1-13.1) per 100,000 population for a 21-year period. Prevalence ratio increase was inversely proportional to age at diagnosis, being null in the >85 years class and maximal in the 25-35 age class (+1700%). Among phenotypes, predominant UMN showed the highest increase (from 0.5, 95% CI 0.3-0.8, to 2.1, 95% CI 1.7 - 2.6, +320%). Discussion: Because of the variability of ALS survival, prevalence ratio strongly depends on the length of the follow-up period. A 12-year period should be sufficient to get a reliable estimate of ALS prevalence including long-survival patients.

7.
NPJ Regen Med ; 6(1): 20, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795700

RESUMO

Transplantation of several types of stem cells (SC) for the treatment of amyotrophic lateral sclerosis (ALS) has been evaluated in numerous Phase I/II clinical trials with inconclusive results. Here, we conducted a meta-analysis to systematically assess the outcome of SC therapy trials which report the evolution of each patient before and after cell administration. In this way, we aimed to determine the effect of the SC intervention despite individual heterogeneity in disease progression. We identified 670 references by electronic search and 90 full-text studies were evaluated according to the eligibility criteria. Eleven studies were included comprising 220 cell-treated patients who received mesenchymal (M) SC (n = 152), neural (N) SC (n = 57), or mononuclear cells (MNC: CD34, CD117, and CD133 positive cells) (n = 11). Our analyses indicate that whereas intrathecal injection of mesenchymal stromal cells appears to have a transient positive effect on clinical progression, as measured by the ALS functional rating score, there was a worsening of respiratory function measured by forced vital capacity after all interventions. Based on current evidence, we conclude that optimal cell product and route of administration need to be determined in properly controlled preclinical models before further advancing into ALS patients. In addition, in-depth understanding of disease mechanisms in subsets of patients will help tailoring SC therapy to specific targets and increase the likelihood of improving outcomes.

8.
Life (Basel) ; 11(4)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920645

RESUMO

Background-Amyotrophic lateral sclerosis (ALS) is a devastating and untreatable motor neuron disease; smoking and alcohol drinking may impact its progression rate. Objective-To ascertain the influence of smoking and alcohol consumption on ALS progression rates. Methods-Cross-sectional multicenter study, including 241 consecutive patients (145 males); mean age at onset was 59.9 ± 11.8 years. Cigarette smoking and alcohol consumption data were collected at recruitment through a validated questionnaire. Patients were categorized into three groups according to ΔFS (derived from the ALS Functional Rating Scale-Revised and disease duration from onset): slow (n = 81), intermediate (80), and fast progressors (80). Results-Current smokers accounted for 44 (18.3%) of the participants, former smokers accounted for 10 (4.1%), and non-smokers accounted for 187 (77.6%). The age of ALS onset was lower in current smokers than non-smokers, and the ΔFS was slightly, although not significantly, higher for smokers of >14 cigarettes/day. Current alcohol drinkers accounted for 147 (61.0%) of the participants, former drinkers accounted for 5 (2.1%), and non-drinkers accounted for 89 (36.9%). The log(ΔFS) was weakly correlated only with the duration of alcohol consumption (p = 0.028), but not with the mean number of drinks/day or the drink-years. Conclusions: This cross-sectional multicenter study suggested a possible minor role for smoking in worsening disease progression. A possible interaction with alcohol drinking was suggested.

9.
Brain Sci ; 11(2)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668641

RESUMO

Telehealth, by definition, is distributing health-related services while using electronic technologies. This narrative Review describes the technological health services (telemedicine and telemonitoring) for delivering care in neurodegenerative diseases, Alzheimer's disease, Parkinson's Disease, and amyotrophic lateral Sclerosis, among others. This paper aims to illustrate this approach's primary experience and application, highlighting the strengths and weaknesses, with the goal of understanding which could be the most useful application for each one, in order to facilitate telehealth improvement and use in standard clinical practice. We also described the potential role of the COVID-19 pandemic to speed up this service's use, avoiding a sudden interruption of medical care.

11.
Neurogenetics ; 22(1): 65-70, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471268

RESUMO

Primary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.


Assuntos
Encefalopatias/genética , Mutação/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Idoso , Encéfalo/metabolismo , Encéfalo/patologia , Encefalopatias/diagnóstico , Encefalopatias/patologia , Éxons/genética , Feminino , Humanos , Linhagem , Fenótipo
12.
NeuroRehabilitation ; 48(1): 49-57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33386822

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. The current practice of caring for patients affected by ALS involves a multidisciplinary team without any indication about oral health care. OBJECTIVE: We sought to investigate the functional status and oral health in patients with ALS to define a specific multidisciplinary management. METHODS: In this cross-sectional study, we included patients affected by ALS, evaluating their functional status, using the Revised ALS Functional Rating Scale (ALSFRS-R) and their oral health status through specific parameters, including Brief Oral Health Status Examination (BOHSE), Winkel Tongue Coating Index (WTCI), and Oral Food Debris Index (OFDI). RESULTS: All 37 patients (mean age: 61.19±11.56 years) showed a poor oral status, independent from the functional status and strictly correlated to the severity of sialorrhea (p = 0.01). OFDI index was negatively correlated with the ALSFRS-R upper limb (p = 0.03). Patients with bulbar onset had significantly lower ability to perform adequate tongue movements in terms of protrusion (p = 0.006) and lateralization (p < 0.001). Significant negative correlations between survival rate and BOHSE (p = 0.03) was found. CONCLUSIONS: Taken together, our findings showed that a poor oral health status might be correlated to a worse functional status and survival time. Thus, an adequate oral health care and rehabilitation should be considered as crucial in the multidisciplinary management of patients with ALS.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Progressão da Doença , Estado Funcional , Saúde Bucal/tendências , Idoso , Esclerose Amiotrófica Lateral/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extremidade Superior/fisiopatologia
13.
Acta Neurol Scand ; 143(5): 489-496, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33185886

RESUMO

BACKGROUND AND OBJECTIVE: Specialized multidisciplinary ALS care has been shown to extend survival and improve patient's and caregiver's quality of life. During the COVID-19 pandemic, the management of patients suddenly changed and telemedicine has been proven to be as effective as outpatient care. We elaborate the experience with Telemedicine of a Tertiary ALS Center from an Italian geographical area with high infectious risk during the COVID-19 pandemic. METHODS: 19 patients were evaluated in telemedicine by a multidisciplinary team including a neurologist (clinical evaluation, intercurrent events, and drug prescriptions); a dietician (diet and weight monitoring); a psychologist (psychological assessment and support); and a physiotherapist (physiotherapy treatment and device prescription). Telemedicine was performed using the online platform "IoMT Connected Care Platform (Ticuro Reply)." RESULTS: All patients reported a positive perception of talking face to face with healthcare professionals and were satisfied with how the team understood their problems. During video televisits, there was a change in the patient's medication regimen in 11/19; 2/19 required pneumological evaluation and started NIV; and 9/16 patients required prescription of devices. The mean monthly decline of ALSFRS-R before televisit was 0.88 (SD 1.17) and during televisit of 0.49 (SD 0.75). Bodyweight and daily caloric content remain stable. Reduction in HADS scores and stability in ALSAQ-40 were observed. DISCUSSION: Our study positively reproduced the multidisciplinary approach currently used with ALS patients, trying to stabilize the functional and metabolic status and improving the psychological one. Future directions include a personalized telemedicine program according to the patient's needs.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/terapia , COVID-19/epidemiologia , Pandemias , Satisfação do Paciente , Telemedicina/métodos , Adulto , Esclerose Amiotrófica Lateral/psicologia , COVID-19/psicologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/normas , Qualidade de Vida/psicologia , Telemedicina/normas
14.
Neurology ; 96(4): e600-e609, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33208543

RESUMO

OBJECTIVE: To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome sequencing in 959 patients with ALS and 677 matched healthy controls. METHODS: We performed genome sequencing in a population-based cohort (Piemonte and Valle d'Aosta Registry for ALS [PARALS]). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population. RESULTS: A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with SOD1, whose rare variants are the second most common cause of disease after C9orf72 expansion. A lower signal was observed for TARDBP, proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited. CONCLUSIONS: We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/genética , Análise Mutacional de DNA/métodos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Vigilância da População , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico , Proteína C9orf72/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Neurol Sci ; 42(3): 1119-1121, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33051751

RESUMO

We found four patients with some characteristic phenotype in our ICU, characterized by focal hypotrophies of the shoulder girdle and the bilateral peroneal district and underlying critical illness neuro-myopathy. In our opinion, these hypotrophies are secondary to the prone position. Is our intention to start early treatment protocol with electrostimulation to evaluate the effectiveness in the prevention of critical illness and focal hypotrophies in ICU SARS-CoV-2 patients, to increase chances of returning to a preinfection functional status.


Assuntos
COVID-19/complicações , Doenças Musculares/virologia , Polineuropatias/virologia , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Decúbito Ventral , SARS-CoV-2
16.
Environ Res ; 192: 110292, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027627

RESUMO

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/etiologia , Esclerose Amiotrófica Lateral/genética , Causalidade , Poluição Ambiental , Humanos , Itália/epidemiologia , Mutação
17.
Brain Sci ; 10(12)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339434

RESUMO

In amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) allows investigation at the microstructural level, employing techniques able to reveal white matter changes. In the current study, a diffusion tensor imaging (DTI) analysis, with a collection of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indexes, was performed in ALS patients to correlate geno- and phenotype features with MRI data, to investigate an in-vivo correlation of different neuropathological patterns. All patients who underwent the MR-DTI analysis were retrospectively recruited. MRI scan was collected within three months from diagnosis. FA and ADC values were collected in corpus callosum (CC), corona radiata (CR), cerebral peduncle (CR), cerebellar peduncle (CbP) and corticospinal tract at posterior limb of internal capsule (CST). DTI analysis performed in the whole ALS cohort revealed significant FA reduction and ADC increase in all selected regions, as widespread changes. Moreover, we observed a higher value of FA in rCR in bulbar patients. A positive correlation between ALS Functional Rating Scale-Revised and FA in rCP was evident. In consideration of the non-invasiveness, the reliability and the easy reproducibility of the method, we believe that brain MRI with DTI analyses may represent a valid tool usable as a diagnostic marker in ALS.

18.
Brain Commun ; 2(2): fcaa124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134918

RESUMO

Despite wide genetic, environmental and clinical heterogeneity in amyotrophic lateral sclerosis, a rapidly fatal neurodegenerative disease targeting motoneurons, neuroinflammation is a common finding. It is marked by local glial activation, T cell infiltration and systemic immune system activation. The immune system has a prominent role in the pathogenesis of various chronic diseases, hence some of them, including some types of cancer, are successfully targeted by immunotherapeutic approaches. However, various anti-inflammatory or immunosuppressive therapies in amyotrophic lateral sclerosis have failed. This prompted increased scrutiny over the immune-mediated processes underlying amyotrophic lateral sclerosis. Perhaps the biggest conundrum is that amyotrophic lateral sclerosis pathogenesis exhibits features of three otherwise distinct immune dysfunctions-excessive inflammation, autoimmunity and inefficient immune responses. Epidemiological and genome-wide association studies show only minimal overlap between amyotrophic lateral sclerosis and autoimmune diseases, so excessive inflammation is usually thought to be secondary to protein aggregation, mitochondrial damage or other stresses. In contrast, several recently characterized amyotrophic lateral sclerosis-linked mutations, including those in TBK1, OPTN, CYLD and C9orf72, could lead to inefficient immune responses and/or damage pile-up, suggesting that an innate immunodeficiency may also be a trigger and/or modifier of this disease. In such cases, non-selective immunosuppression would further restrict neuroprotective immune responses. Here we discuss multiple layers of immune-mediated neuroprotection and neurotoxicity in amyotrophic lateral sclerosis. Particular focus is placed on individual patient mutations that directly or indirectly affect the immune system, and the mechanisms by which these mutations influence disease progression. The topic of immunity in amyotrophic lateral sclerosis is timely and relevant, because it is one of the few common and potentially malleable denominators in this heterogenous disease. Importantly, amyotrophic lateral sclerosis progression has recently been intricately linked to patient T cell and monocyte profiles, as well as polymorphisms in cytokine and chemokine receptors. For this reason, precise patient stratification based on immunophenotyping will be crucial for efficient therapies.

20.
Stem Cell Res ; 47: 101924, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739880

RESUMO

Among the known causative genes of familial ALS, SOD1mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function. In order to better understand the pathogenic mechanisms of SOD1 mutation, a human induced pluripotent stem cell (hiPSC) line was generated from the somatic cells of a female patient carrying a missense variation in SOD1 (L145F).

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