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—A limitation of many compressive imaging archi-tectures lies in the sequential nature of the sensing process, which leads to long sensing times. In this paper we present a novel architecture that uses fewer detectors than the number of reconstructed pixels and is able to acquire the image in a single acquisition. This paves the way for the development of(More)
Short-hairpin RNA (shRNA)-mediated gene knockdown is a powerful tool for targeted gene silencing and an emerging novel therapeutic strategy. Recent publications, however, reported unexpected toxicity after utilizing viral-mediated shRNA knockdown in vivo. Thus, it is currently unclear whether shRNA-mediated knockdown strategy can be used as a safe and(More)
The cellular hallmarks of Parkinson's disease (PD) are the loss of nigral dopaminergic neurons and the formation of α-synuclein-enriched Lewy bodies and Lewy neurites in the remaining neurons. Based on the topographic distribution of Lewy bodies established after autopsy of brains from PD patients, Braak and coworkers hypothesized that Lewy pathology primes(More)
In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed. The disease was considered to be limited to the basal ganglia, but recent studies have suggested a more widespread pathology involving hypothalamic dysfunction. Here we tested the hypothesis that expression of mutant huntingtin in the hypothalamus causes metabolic(More)
Impairments in the capacity of dopaminergic neurons to handle cytoplasmic dopamine may be a critical factor underlying the selective vulnerability of midbrain dopamine neurons in Parkinson's disease. Furthermore, toxicity of α-synuclein in dopaminergic neurons has been suggested to be mediated by direct interaction between dopamine and α-synuclein through(More)
Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein(More)
Viral vector-mediated gene transfer utilizing adeno-associated viral vectors has recently entered clinical testing as a novel tool for delivery of therapeutic agents to the brain. Clinical trials in Parkinson's disease using adeno-associated viral vector-based gene therapy have shown the safety of the approach. Further efforts in this area will show if(More)
In vivo gene transfer using viral vectors is an emerging therapy for neurodegenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the(More)
Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown.(More)
Dopamine replacement for Parkinson's disease (PD) have seen three major iterations of improvements since the introduction of l-3,4-dihydroxyphenylalanine (l-DOPA) pharmacotherapy: dopamine receptor agonists, ex vivo gene transfer for cell transplantation and most recently in vivo gene therapy. In this chapter, we describe the principles behind viral(More)