In Huntingtons disease, it is huntingtin.Transglutaminase substrates:
Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of transglutaminases in vitro or in vivo, that is, they can be bonded by trasglutaminases by covalent bonds to each other and potentially to any other transglutaminase substrate in the brain.Transglutaminase augmented expression:
It has been proved that in these neurodegenerative diseases (Alzheimers disease, Parkinsons disease, and Huntingtons disease) the expression of the transglutaminase enzyme is increased.Presence of isopeptide bonds in these structures:
The presence of isopeptide bonds (the result of the transglutaminase reaction) have been detected in the abnormal structures that are characteristic of these neurodegenerative diseases.Co-localization:
Co-localization of transglutaminase mediated isopeptide bonds with these abnormal structures has been detected in the autopsy of brains of patients with these diseases. Management
The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. Animal models in research
In the search for effective treatments (as opposed to palliative care), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimers disease, and also phase II clinical trials for use in Huntingtons disease.
Pai syndrome, also known as Median cleft of the upper lip-corpus callosum lipoma-midline facial cutaneous polyps syndrome, is a very rare genetic disorder which is characterized by nervous system, cutaneous, ocular, nasal and bucal anomalies with facial dysmorphisms. Signs and symptoms
List of common symptoms:
Depressed nasal bridge
Median cleft lip
Central nervous system lipomas. Nasal polyposis
Presence of skin tags
Subcutaneous noduleList of not-so-common symptoms:[2]

Oral frenulum abnormalities
Bifid uvula
Hypertelorism
TelecanthusList of uncommon symptoms:[2]

Missing/underdeveloped corpus callosum
Down-slanting parpebral fissures
Encephalocele
Coloboma
Nose defects
Frontal bossing
High palate

Causes
A specific, shared genetic cause hasnt been found. The closest thing to it was a case reported by Masuno et al. of a Japanese girl with symptoms of the disorder plus short stature and intellectual disabilities with a spontaneous reciprocal translocation. This translocation involved chromosome Xq28 and chromosome 16q11.2 (more specifically, 46,X,t(X;16)(q28;q11.2). Epidemiology
According to OMIM, 18 cases have been described in medical literature, but according to ORPHAnet, 67 cases have been described. == References ==