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Recent studies delineate a pathway involving familial Parkinson's disease (PD)-related proteins PINK1 and Parkin, in which PINK1-dependent mitochondrial accumulation of Parkin targets depolarized mitochondria towards degradation through mitophagy. The pathway has been primarily characterized in cells less dependent on mitochondria for energy production than(More)
The modulation of utrophin gene expression in muscle by the nerve-derived factor agrin plausibly involves the trophic factor ARIA/heregulin. Here we show that heregulin treatment of mouse and human cultured myotubes caused a approximately 2.5-fold increase in utrophin mRNA levels. Transient transfection experiments with utrophin promoter-reporter gene(More)
This article describes a method to quantify the movements of larval zebrafish in multiwell plates, using the open-source MATLAB applications LSRtrack and LSRanalyze. The protocol comprises four stages: generation of high-quality, flatly illuminated video recordings with exposure settings that facilitate object recognition; analysis of the resulting(More)
Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close(More)
Duchenne muscular dystrophy is a prevalent X-linked neuromuscular disease for which there is currently no cure. Recently, it was demonstrated in a transgenic mouse model that utrophin could functionally compensate for the lack of dystrophin and alleviate the muscle pathology (Tinsley, J. M., Potter, A. C., Phelps, S. R., Fisher, R., Trickett, J. I., and(More)
Multiple convergent lines of evidence implicate both α-synuclein (encoded by SCNA) and mitochondrial dysfunction in the pathogenesis of sporadic Parkinson's disease (PD). Occupational exposure to the mitochondrial complex I inhibitor rotenone increases PD risk; rotenone-exposed rats show systemic mitochondrial defects but develop specific neuropathology,(More)
α-Synuclein is strongly implicated in the pathogenesis of Parkinson disease. However, the normal functions of synucleins and how these relate to disease pathogenesis are uncertain. We characterized endogenous zebrafish synucleins in order to develop tractable models to elucidate the physiological roles of synucleins in neurons in vivo. Three zebrafish(More)
Zebrafish models of human neuropsychiatric diseases offer opportunities to identify novel therapeutic targets and treatments through phenotype-based genetic or chemical modifier screens. In order to develop an assay to detect rescue of zebrafish models of Parkinsonism, we characterized spontaneous zebrafish larval motor behavior from 3 to 9 days post(More)
Duchenne muscular dystrophy (DMD) is an inherited muscle-wasting disease caused by the absence of a muscle cytoskeletal protein, dystrophin. We have previously shown that utrophin, the autosomal homologue of dystrophin, is able to compensate for the absence of dystrophin in a mouse model of DMD; we have therefore undertaken a detailed study of the(More)
The aim of this study was to isolate cis-acting regulatory elements for the generation of transgenic zebrafish models of neurodegeneration. Zebrafish enolase-2 (eno2) showed neuronal expression increasing from 24 to 72 h post-fertilization (hpf) and persisting through adulthood. A 12 kb eno2 genomic fragment, extending from 8 kb upstream of exon 1 to exon(More)