Advanced search    

Search: authors:"Hua Li"

13 papers found.
Use AND, OR, NOT, +word, -word, "long phrase", (parentheses) to fine-tune your search.

Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice

Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative...

Aggregation of N-Terminal Huntingtin is Dependent on the Length of Its Glutamine Repeats

Shi-Hua Li 0 Xiao-Jiang Li 0 0 Department of Genetics, Emory University School of Medicine , Atlanta, GA 30322, USA Huntington's disease (HD) is caused by expansion of a glutamine repeat in

Abnormal association of mutant huntingtin with synaptic vesicles inhibits glutamate release

In Huntington disease (HD), polyglutamine expansion causes the disease protein huntingtin to aggregate and accumulate in the nucleus and cytoplasm. The cytoplasmic huntingtin aggregates are found in axonal terminals and electrophysiological studies show that mutant huntingtin affects synaptic neurotransmission. However, the biochemical basis for huntingtin-mediated synaptic...

Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice

A pathological hallmark of polyglutamine diseases is the presence of inclusions or aggregates of the expanded polyglutamine protein. Polyglutamine inclusions are present in the neuronal nucleus in a number of inherited neurodegenerative disorders, including Huntington disease (HD). Recent studies suggest that polyglutamine inclusions may sequester polyglutamine-containing...

Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis

Expansion of a polyglutamine repeat in huntingtin causes Huntington’s disease (HD). Although full-length huntingtin is predominantly distributed in the cytoplasm, N-terminal fragments of huntingtin with expanded polyglutamine tracts are able to accumulate in the nucleus and kill neurons through apoptotic pathways. Transgenic mice expressing N-terminal mutant huntingtin show...

Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations

NODAL and its signaling pathway are known to play a key role in specification and patterning of vertebrate embryos. Mutations in several genes encoding components of the NODAL signaling pathway have previously been implicated in the pathogenesis of human left–right (LR) patterning defects. Therefore, NODAL, a member of TGF-β superfamily of developmental regulators, is a strong...

Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease

A polyglutamine repeat expansion of more than 36 units in a protein called huntingtin (htt) is the only known cause of Huntington's disease (HD). The expanded repeat length is inversely correlated with the age-at-onset (AAO), however, the onset age among HD patients with CAG repeats below 60 units varies considerably. In addition to environmental factors, genetic factors...

Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36

Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. Eight million Americans over the age of 50 have osteoporosis of the femoral neck. The most important risk factor for osteoporosis is low bone mineral density (BMD), and several epidemiological studies have shown the importance of genetic factors in determining...

Ultrastructural Localization and Progressive Formation of Neuropil Aggregates in Huntington's Disease Transgenic Mice

Human Molecular Genetics Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice He Li 0 Shi-Hua Li 0 Anna L. Cheng 0 Laura Mangiarini 0

Mutation at the Anophthalmia White Locus in Syrian Hamsters: Hploinsufficiency in the Mitf Gene Mimics Human Waardenburg Syndrome Type 2

Mutations in MITF (microphthalmia transcription factor) cause Waardenburg syndrome type 2 (WS2A) in humans, an autosomal dominant disorder consisting of deafness and hypopigmentation. Phenotypes vary significantly within WS2 pedigrees, and there is generally no correlation between the predicted biochemical properties of mutant MITF proteins and disease severity. We have...

Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease

In postmortem Huntington's disease brains, mutant htt is present in both nuclear and cytoplasmic compartments. To dissect the impact of nuclear and extranuclear mutant htt on the initiation and progression of disease, we generated a series of transgenic mouse lines in which nuclear localization or nuclear export signal sequences have been placed N-terminal to the htt exon 1...

Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome

Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment elevation in leads V1–V3 and sudden death due to ventricular fibrillation, identical to that seen in Brugada syndrome. We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as...

Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice

Huntington’s disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons. In precise genetic models of juvenile HD, HdhQ92 and HdhQ111 knock-in mice, long polyglutamine segments change huntingtin’s physical properties, producing HD-like in vivo correlates in the...