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Enrique Luengo Izaskun Buendia Cristina Fernndez‐Mendívil Paula Trigo‐Alonso Pilar Negredo Patrycja Michalska Borja Hernndez‐García Cristina Snchez‐Ramos Juan A. Bernal Tsuneya Ikezu Rafael Len Manuela G. Lpez 《Journal of pineal research》2019,67(1)
Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD. 相似文献
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Maria Gonzalez-Cao Cristina Carrera Juan Francisco Rodriguez Moreno Pedro Rodríguez-Jiménez Mónica Antoñanzas Basa Rosa Feltes Ochoa Teresa Puertolas Eva Muñoz-Couselo José Luis Manzano Ivan Marquez-Rodas Juan Martín-Liberal Ainara Soria Pilar Lopez Criado Almudena Garcia-Castaño Aram Boada Pablo Ayala de Miguel Susana Puig Guillermo Crespo Alfonso Berrocal 《Journal of the American Academy of Dermatology》2021,84(5):1412-1415
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Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
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Jos M. Martín Encarnacion Montesinos Pilar Cordero Victor Gonzalez Dolores Ramon 《Pediatric dermatology》2019,36(2):265-267
Trichotillomania is a form of traction alopecia resulting from repetitive and compulsive hair pulling and plucking. Trichotillomania and patchy alopecia areata may have similar clinical and dermoscopic features in some cases. On trichoscopic examination, the presence of black dots, coiled or hook hair, shafts of varying lengths with fraying or split ends (trichoptilosis), and an absence of exclamation mark hairs and yellow dots are suggestive of trichotillomania. 相似文献
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María Cabrerizo Gloria Trallero María José Pena Amaia Cilla Gregoria Megias Carmen Mu?oz-Almagro Eva Del Amo Diana Roda Ana Isabel Mensalvas Antonio Moreno-Docón Juan García-Costa Nuria Rabella Manuel Ome?aca María Pilar Romero Sara Sanbonmatsu-Gámez Mercedes Pérez-Ruiz María José Santos-Mu?oz Cristina Calvo And the study group of “Enterovirus parechovirus infections in children under ?years-old Spain” PI- 《European journal of pediatrics》2015,174(11):1511-1516
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Vincent Laville Sigrid Le Clerc Khaled Ezzedine Randa Jdid Lieng Taing Toufik Labib Cdric Coulonges Damien Ulveling Pilar Galan Christiane Guinot Leopold Fezeu Frdrique Morizot Julie Latreille Denis Malvy Erwin Tschachler Jean‐Franois Zagury 《Experimental dermatology》2019,28(8):892-898
Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10‐10) and rs4746957 (P = 1.06 × 10‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity. 相似文献
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