RESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find a cure, no proper treatment has been developed yet, and the only effective countermeasure is to prevent the disease progression by early diagnosis. The reason why new drug candidates fail to show therapeutic effects in clinical studies may be due to misunderstanding the cause of AD. Regarding the cause of AD, the most widely known is the amyloid cascade hypothesis, in which the deposition of amyloid beta and hyperphosphorylated tau is the cause. However, many new hypotheses were suggested. Among them, based on preclinical and clinical evidence supporting a connection between AD and diabetes, insulin resistance has been pointed out as an important factor in the development of AD. Therefore, by reviewing the pathophysiological background of brain metabolic insufficiency and insulin insufficiency leading to AD pathology, we will discuss how can insulin resistance cause AD.
Assuntos
Doença de Alzheimer , Resistência à Insulina , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Resistência à Insulina/fisiologia , InsulinaRESUMO
In this study, we investigated the effect of a random nanostructure scattering layer (RSL) on the microcavity and light extraction in organic light emitting diodes (OLEDs). In the case of the conventional OLED, the optical properties change with the thickness of the hole transporting layer (HTL) because of the presence of a microcavity. However, OLEDs equipped with the an RSL showed similar values of external quantum efficiency and luminous efficacy regardless of the HTL thickness. These phenomena can be understood by the scattering effect because of the RSL, which suppresses the microcavity effect and extracts the light confined in the device. Moreover, OLEDs with the RSL led to reduced spectrum and color changes with the viewing angle.
RESUMO
In the present study, we investigated whether a histone deacetylase sirtuin 1 (SIRT1) can regulate the protein stability of homeodomain-interacting protein kinase 2 (HIPK2). We observed the evidence of molecular interaction between SIRT1 and HIPK2. Interestingly, overexpression or pharmacological activation of SIRT1 promoted ubiquitination and the proteasomal degradation of HIPK2 whereas inhibition of SIRT1 activity increased the protein level of HIPK2. Furthermore, a SIRT1 activator decreased the level of HIPK2 acetylation whereas an inhibitor increased the acetylation level. These results suggest that SIRT1 may deacetylate and promote the ubiquitination and subsequent proteasomal degradation of HIPK2.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Sirtuína 1/metabolismo , Células HEK293 , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Estabilidade Proteica , Proteólise , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/genética , UbiquitinaçãoRESUMO
Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson's disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.
Assuntos
Apoptose , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Heptacloro/farmacologia , Inseticidas/farmacologia , Mitocôndrias/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Neurônios Dopaminérgicos/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo.
Assuntos
Apoptose , Neurônios Dopaminérgicos/efeitos dos fármacos , Heptacloro/toxicidade , Locomoção , Praguicidas/toxicidade , Substância Negra/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Linhagem Celular Tumoral , Células Cultivadas , Neurônios Dopaminérgicos/patologia , Marcha , Humanos , Camundongos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Transtornos Parkinsonianos/induzido quimicamente , Substância Negra/patologia , Substância Negra/fisiopatologiaRESUMO
A random scattering layer (RSL) consisting of a random nano-structure (RNS) and a high refractive index planarization layer (HRI PL) is suggested and demonstrated as an efficient internal light-extracting layer for transparent organic light emitting diodes (TOLEDs). By introducing the RSL, a remarkable enhancement of 40% and 46% in external quantum efficiency (EQE) and luminous efficacy (LE) was achieved without causing deterioration in the transmittance. Additionally, with the use of the RSL, the viewing angle dependency of EL spectra was reduced to a marginal degree. The results were interpreted as the stronger influence of the scattering effect over the microcavity. The RSL can be applied widely in TOLEDs as an effective light-extracting layer for extracting the waveguide mode of confined light at the indium tin oxide (ITO)/OLED stack without introducing spectral changes in TOLEDs.