Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease
Funny turns and chest pain – funny turns are an unusual presentation for
cardiac disease in children, much more commonly associated with simple
faints, or neurological disease such as epilepsy. Sudden collapse may be due to
arrhythmias, and collapse with exercise is a very worrying sign in a child with
significant left ventricular outflow tract obstruction such as aortic stenosis.
Most chest pain in children is due to musculoskeletal problems, especially in
older children. Coronary artery abnormalities, and hence chest pain due to
angina, is rare.
Almost half of the patients experience arthritis in the hips or the shoulders. Up to 30% of the
patients suffer from small joint involvement with swelling, pain and stiffness in the
inflamed joints. Often these appear as asymmetrical oligoarthritis. Usually they are non-
erosive, but deformity and consequently destruction of the hips have been seen. An early
involvement of peripheral joints can be an indicator of a more aggressive progress.
Peripheral joint involvement can occur at any stage of the disease (Sieper J, Braun J,
Rudwaleit M, Boonen A, Zink A) (Gladman DD). ...
The neurons of the corpus striatum receive an excitatory input from the cerebral cortex and the thalamus.
The major outputs project to the globus pallidus and the substantia nigra pars reticula (SNr), and use
gamma-aminobutyric acid (GABA) as a transmitter. Major efferent pathways from the globus pallidus
interna and the SNr project to the thalamus. Feedback to the striatum is through the dopaminergic
striatonigral pathway originating in the substantia nigra pars compacta (SNc; Figure 1).
These separate pathways utilize different neuropeptides and dopamine receptors.
Nucleotide Repeat Expansion Disorders
Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold (Table 62-6). The repeats are sometimes located within the coding region of the genes, as in Huntington disease or the X-linked form of spinal and bulbar muscular atrophy (SBMA, Kennedy syndrome). In other instances, the repeats probably alter gene regulatory sequences. If an expansion is present, the DNA fragment is unstable and tends to expand further during cell division.
How variations in genes contribute to variations in disease risk has
been a subject of study for more than 100 years (IOM, 2006). Until fairly
recently research focused on single genes that give rise to rare genetic diseases
such as cystic fibrosis or Huntington’s disease.
A large number of neurodegenerative diseases in humans result from pro-tein misfolding and aggregation. Protein misfolding is believed to be the
primary cause of Alzheimer’s disease, Parkinson’s disease, Huntington’s
disease, Creutzfeldt–Jakob disease, cystic fibrosis, Gaucher’s disease and
many other degenerative and neurodegenerative disorders.
Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a b-lactam antibiotic that increases GLT1 expression. Only at advanced ages ( 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s.
After the successful cloning of the first gene for a polyglutamine disease in
1991, the expanded polyglutamine tract in the nine polyglutamine disease
proteins became an obvious therapeutic target. Early hypotheses were that
misfolded, precipitated protein could be a universal pathogenic mechanism.
However, new data are accumulating on Huntington’s disease and other
polyglutamine diseases that appear to contradict the toxic aggregate
Autophagy is a nonspecific bulk degradation pathway for long-lived cyto-plasmic proteins, protein complexes, or damaged organelles. This process is
also a major degradation pathway for many aggregate-prone, disease-cau-sing proteins associated with neurodegenerative disorders, such as mutant
huntingtin in Huntington’s disease. I
Huntingtin protein (Htt), whose mutation causes Huntington’s disease
(HD), interacts with large numbers of proteins that participate in diverse
cellular pathways. This observation indicates that wild-type Htt is involved
in various cellular processes and that the mutated Htt alters these processes
Recently, we reported that the transient expression of huntingtin exon1
polypeptide containing polyglutamine tracts of various sizes (httEx1-polyQ)
in cell models of Huntington disease generated an oxidative stress whose
intensity was CAG repeat expansion-dependent.
Huntington’s disease (HD) is a progressive neurodegenerative disorder
characterized by multifarious dysfunctional alterations including mitochon-drial impairment. In the present study, the formation of inclusions caused
by the mutation of huntingtin protein and its relationship with changes in
energy metabolism and with pathological alterations were investigated both
in transgenic and 3-nitropropionic acid-treated mouse models for HD.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Connecting the dots in Huntington’s disease with protein interaction networks...
Neurodegenerative disorders are common and devastating. Rationally, the most
effective treatments will target pathogenetic mechanisms. While alternative approaches,
based on alleviating the symptoms of patients with Alzheimer disease,
Parkinson disease, Huntington disease, prion disorders or amyotrophic lateral sclerosis,
can be expected to reduce suffering, studies of pathogenesis of these agerelated
disorderswill be most important for enabling early diagnosis and the creation
of preventative and curative treatments.
Loss of cannabinoid receptors (CB1) occurs prior to neuro-degeneration in Huntington’s disease (HD). The levels and
distribution of CB1 RNA were equivalent in 3-week-old
mice regardless of genotype demonstrating that the specific
factors and appropriate chromatin structure that lead to the
transcription ofCB1were present in the striatum of young
R6/2 and R6/1 transgenic HD mice.
Neurodegenerative disorders, such as Huntington’s, Alzheimer’s, and
Parkinson’s diseases, affect millions of people worldwide and currently there
are few effective treatments and no cures for these diseases. Transgenic mice
expressing human transgenes for huntingtin, amyloid precursor protein, and
other genes associated with familial forms of neurodegenerative disease in
humans provide remarkable tools for studying neurodegeneration because
they mimic many of the pathological and behavioural features of the human