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Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were(More)
Transient cerebral ischemia leads to irreversible translational inhibition which has been considered as a hallmark of delayed neuronal death after ischemia. This study utilized a rat transient cerebral ischemia model to investigate whether irreversible translational inhibition is due to abnormal aggregation of translational complex, i.e. the ribosomes and(More)
Huntington's disease (HD) is an autosomal dominant disorder characterized by involuntary movements, dementia, and progressive, global, but regionally accentuated, brain atrophy. The disease affects the striatum most severely. An expansion of a trinucleotide repeat on chromosome 4p16.3 within the coding region of a gene termed IT15 has been identified as the(More)
Previous studies have shown that in advanced cases of Huntington's disease, enkephalin-immunoreactive striatal projections to the external globus pallidus may be more affected than substance P-containing striatal projections to the inner segment of the pallidum [Reiner A. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 5733-5737]. Other immunohistochemical(More)
CAG repeat expansion in the Huntington's disease gene (HD) was examined in postmortem brains from 310 clinically diagnosed and 15 'at risk' individuals. Presence of an expanded CAG allele (>37 units) was the cause of the disorder in almost all cases (307 of 310). Despite a diversity of reporting clinicians, neurological and psychiatric onset and age at(More)
In Huntington's disease striatal neurons undergo marked changes in dendritic morphology and coincidently exhibit an increase in immunoreactive calbindin D28k (calbindin), a cytosolic calcium-binding protein which is highly abundant in these neurons. Previous studies in the rat striatum have shown that excitotoxic injury, which is linked to a rise in(More)
We describe two protocols for preparing human brains collected for research and diagnosis. In both protocols, one half brain is processed for research and the other for neuropathological evaluation. Clinical, neuropathological and tissue mRNA retention data are used for sample categorization. In protocol 1, coronal, whole hemisphere slices cut at(More)
Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation(More)
Aggregation of α-synuclein contributes to the formation of Lewy bodies and neurites, the pathologic hallmarks of Parkinson disease (PD) and α-synucleinopathies. Although a number of human mutations have been identified in familial PD, the mechanisms that promote α-synuclein accumulation and toxicity are poorly understood. Here, we report that hyperactivity(More)
Seven cases of Huntington's disease (HD) showing unusual neostriatal findings are reported. In these patients, the neostriatum contained scattered islets of relatively intact parenchyma. We attempted to determine whether these cases might represent a clinico-pathological entity, and also sought to acquire a better understanding of the neostriatal(More)