RESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder generally manifesting in the first few years of life and tending to persist into adolescence and adulthood. It is characterized by deficits in communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities. It is a disorder with multifactorial etiology. In this chapter, we will focus on the most important and common epidemiological studies, pathogenesis, screening, and diagnostic tools along with an explication of genetic testing in ASD.
Assuntos
Transtorno do Espectro Autista , Adolescente , Adulto , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Criança , HumanosRESUMO
Huntington's disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia). Mutation in either of the two copies of a gene called huntingtin (HTT), which codes genetic information for a protein called "huntingtin (Htt)", precipitates the disease in an individual. Expansion of cytosine-adenine-guanine (CAG) triplet repeats in the HTT gene results in an abnormal Htt protein. Intracellular neuronal accumulation of the mutated Htt protein (mHtt) causes distinctive erratic movements associated with HD. Further, excessive accumulation of the HTT gene repeats causes abnormal production of reactive oxygen species (ROS) and the ensuing mitochondrial (MT) oxidative stress in neurons. Since there is neither a cure nor a promising strategy to delay onset or progression of HD currently available, therapeutics are mainly focusing only on symptomatic management. Several studies have shown that MT dysfunction-mediated oxidative stress is a key factor for the neurodegeneration observed in HD. Supplementation of antioxidants and nutraceuticals has been widely studied in the management of oxidative damage, an associated complication in HD. Therefore, various antioxidants are used as therapeutics for managing and/or treating HD. The present review aimed at delving into the abnormal cellular changes and energy kinetics of the neurons expressing the mHtt gene and the therapeutic roles of antioxidants in HD.
Assuntos
Antioxidantes/uso terapêutico , Doença de Huntington/terapia , Fármacos Neuroprotetores/uso terapêutico , Animais , Humanos , Doença de Huntington/metabolismoRESUMO
We have developed an affinity-precipitation technique to facilitate conducting glutathione S-transferase (GST) pull-down assays. The dehydrated immobilized glutathione resin format, when combined with microcentrifuge spin columns, is a powerful tool that enables the simultaneous performance of resin hydration, the binding of the GST fusion protein, and the pull-down step with the appropriate protein partner in a semihigh-throughput fashion (multiple samples processed at the same time). The entire assay process is shortened and recovery is enhanced when coupled with a spin-column format, providing a convenient way to study protein-protein interactions. We successfully tested the resin format/technique in three common pull-down applications utilizing radiolabeled, overexpressed, and activated endogenous interacting protein partners.