Three D4S10 restriction-fragment-length polymorphisms produced by the HindIII, EcoRI, and Bg/I enzymes were used for all tests, and the probability that a subject was a Huntington's disease carrier was calculated.
Actin bundling protein 34 (ABP34) is the one of 11 actin-crosslinking proteins identified in Dictyostelium discoideum, a novel model organism for the study of actin-associated neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.
Expression of IT15 is not reduced in the brain of HD patients when corrected for actin (though it is slightly decreased in the striatum when uncorrected, consistent with neuronal loss).
By live cell fluorescence lifetime imaging measurement-Förster resonant energy transfer studies and western blot assays, we quantitatively observed that stress-activated tissue transglutaminase 2 (TG2) is responsible for the actin-cofilin covalent cross-linking observed in HD.
We propose a mechanism for mitochondrial dysfunction in our yeast model of HD in which the interactions of misfolded/aggregated polyglutamine domains with the mitochondrial and actin networks lead to disturbances in mitochondrial distribution and function and to increase in ROS production.
Diagnostic and predictive testing for Huntington disease (HD) requires an accurate determination of the number of CAG repeats in the Huntingtin (HHT) gene.
In considering whether presymptomatic Huntington's individuals have a disability under the ADA, an analogy is made between Huntington's disease and HIV-positive status.
We found diminished intracellular ATP concentration (22.5 ± 1.7 in HD; 29.3 ± 1.4 nmol/mg protein in control), increased ADA activity (27.9 ± 1.0 in HD; 21.1 ± 1.6 nmol/min/mg protein in control) and reduced activities of eNTPD (2.4 ± 0.5 in HD; 5.8 ± 0.7 nmol/min/mg protein in control), e5NT (0.1 ± 0.01 in HD; 0.2 ± 0.01 nmol/min/mg protein in control) and eADA (0.3 ± 0.03 in HD; 0.4 ± 0.04 nmol/min/mg protein in control) while NAD<sup>+</sup> concentration, AMPD and PNP activities remained unchanged.
Taken together, these results point to a detrimental role of hyperactive ADAM10 at the HD synapse and provide preclinical evidence of the therapeutic potential of ADAM10 inhibition in HD.
First, we observed a hippocampal decline of all three PACAP receptor expressions, i.e., PAC1, VPAC1, and VPAC2, in two different HD mouse models, R6/1 and HdhQ7/Q111, from the onset of cognitive dysfunction.
In the central nervous system, PACAP has been shown to have in vivo protective effects in models of cerebral ischemia, Parkinson's and Alzheimer's disease, Huntington chorea, traumatic brain and spinal cord injury and different retinal pathologies.
Taken together, these results suggest that PACAP, acting through stimulation of PAC1 receptor, may have a therapeutic potential to counteract cognitive deficits induced in HD.
The alpha-adducin gene maps immediately telomeric to D4S95, in a region likely to contain the HD defect, and must be scrutinized to establish whether it is the site of the HD mutation.
The murine homologues of the Huntington disease gene (Hdh) and the alpha-adducin gene (Add1) map to mouse chromosome 5 within a region of conserved synteny with human chromosome 4p16.3.
Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients.
Moreover, post-HD body weight (β = -.274, p = .041), waist circumference (β = -.311, p < .001), logarithmically transformed triglyceride level (log-TG; β = -.186, p = .031), and log-glucose (β = -.225, p = .008) were negatively associated with adiponectin levels in HD patients after multivariable forward stepwise linear regression analysis.
Additionally, we identified new associations in the same gene, thus further supporting the potential contribution of ADORA2A to the pathogenesis of HD.