Endogenous TARBP2 promotes metastatic cell invasion and colonization by destabilizing amyloid precursor protein (APP) and ZNF395 transcripts, two genes previously associated with Alzheimer's and Huntington's disease, respectively.
To explain these results, it was suggested that the HD locus (HD) lies close to the telomere and that a recombination event took place between HD and the most telomeric marker examined, D4S90.
Twelve Italian families with Huntington disease were tested with 10 probes known to be linked to the disease locus and able to detect polymorphisms at the following loci on chromosome 4: D4S10, D4S127, D4S95, D4S43, D4S115, D4S111, D4S90.
D4S95 is a most useful DNA marker for predictive testing programs, while D4S90 will serve as a useful starting point for identifying DNA fragments closer to the gene for HD.
Allelic frequencies of RFLPs at loci closely linked to the HD gene, D4S95, D4S91, D4S141, and D4S90, were determined in 13 Huntington's disease (HD) patients from nine Chinese families and 129 normal subjects.
These data suggest that it may be possible to construct high and low risk haplotypes, which may be helpful in DNA analysis and genetic counselling for HD, and represent independent evidence that the gene for HD is centromeric to more distally located DNA markers such as D4S90.
Together, we propose that Wig1, a key p53 downstream molecule in HD condition, play an important role in stabilizing mutant Htt mRNA and thereby accelerating HD pathology in the mHtt-p53-Wig1 positive feedback manner.
Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.
Palmitoylation of CASP6 is decreased both in Hip14<sup>-/-</sup> mice, where HIP14is absent, and in YAC128 mice, a model of Huntington disease, where HIP14 is dysfunctional and where CASP6 activity is increased.
Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD.
Our findings suggest that decreased interaction between htt and HIP14 could contribute to the neuronal dysfunction in HD by perturbing normal intracellular transport pathways in neurons.
Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.
In total six PATs (HIP14, HIP14L, ZDHHC8, ZDHHC9, ZDHHC12, and ZDHHC15) and one thioesterase (PPT1) have been implicated in Huntington disease (HD), Alzheimer disease, schizophrenia, mental retardation, and infantile and adult onset forms of neuronal ceroid lipofuscinosis.
In addition, HIP14L interacts less with mutant HTT than the wild-type protein, suggesting that reduced HIP14L-dependent palmitoylation of neuronal substrates may contribute to the pathogenesis of HD.
This suggests that altered HIP14-HTT and HIP14L-HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates.
This is accompanied by reduced autophagy (accumulation of p62) as the consequence of increased ZBTB16 expression and reduced ULK1 activity, as we have previously observed in Huntington's disease (HD).
In order to assess whether single-nucleotide polymorphisms (SNPs) in the OGG1 and XPC genes, both implicated in responses to oxidative stress, are associated with the age of onset of HD, 9 SNPs have been genotyped in 299 individuals with HD and 582 controls.