Learn More
Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein. To gain insight into the pathogenesis of HD, we generated transgenic mice that express a cDNA encoding an N-terminal fragment (171 amino acids) of huntingtin with 82, 44 or 18 glutamines. Mice(More)
Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required(More)
To examine the mechanism through which neurofilaments regulate the caliber of myelinated axons and to test how aberrant accumulations of neurofilaments cause motor neuron disease, mice have been constructed that express wild-type mouse NF-H up to 4.5 times the normal level. Small increases in NF-H expression lead to increased total neurofilament content and(More)
Huntington's disease (HD) is caused by CAG triplet repeat expansion in IT15 which leads to polyglutamine stretches in the HD protein product, huntingtin. The pathological hallmark of HD is the degeneration of subsets of neurons, primarily those in the striatum and neocortex. Specific morphological markers of affected cells have not been identified in(More)
Approximately 10% of cases of Alzheimer's disease are familial and associated with autosomal dominant inheritance of mutations in genes encoding the amyloid precursor protein, presenilin 1 (PS1) and presenilin 2 (PS2). Mutations in PS1 are linked to about 25% of cases of early-onset familial Alzheimer's disease. PS1, which is endoproteolytically processed(More)
Each of the glutamine repeat neurodegenerative diseases has a particular pattern of pathology largely restricted to the CNS. However, there is considerable overlap among the regions affected, suggesting that the diseases share pathogenic mechanisms, presumably involving the glutamine repeats. We focus on Huntington's disease (HD) and(More)
The protein huntingtin (htt), aggregated in neuronal nuclear inclusions, is pathognomonic of Huntington's disease (HD). Constructs, translated in vitro from the N terminus of htt, containing either polyQ23 from a normal individual, or polyQ41 or polyQ67 from an HD patient, were all soluble. Transglutaminase (TGase) crosslinked these proteins, and the(More)
Huntington's disease (HD) is an inherited neurodegenerative disorder associated with expansion of a CAG repeat in the IT15 gene. The IT15 gene is translated to a protein product termed huntingtin that contains a polyglutamine (polyGln) tract. Recent investigations indicate that the cause of HD is expansion of the polyGln tract. However, the function of(More)
Transglutaminase (TGase) activity is increased in affected regions of brains from patients with Huntington's disease (HD). TGase activity is particularly elevated in the nucleus compared with the cytoplasm from these brains. Gamma-glutaminyl-lysyl cross-links have been detected in nuclear inclusions in HD brain, indicating that TGase may play a prominent(More)
In the neocortices and amygdalae of young and aged macaques, cholinergic axons were identified by means of a monoclonal antibody to bovine choline acetyltransferase. Many fine, linear, immunoreactive profiles were seen in these animals. In the older animals, some cholinergic axons showed multifocal enlargements along their course. In some instances,(More)