Ubiquitin, and the biological pathways of this protein, has been associated with the pathogenesis of certain diseases. Additionally, it is also thought to be beneficial in the diagnosis certain conditions, acting as a biological marker.
Neurodegenerative disorders are linked most strongly to abnormalities in the presence and function of ubiquitin, although there are several other syndromes that are also associated with the protein pathway.
Physiological Function
Prior to linking ubiquitin to certain diseases, it is essential that there is a comprehensive understanding of the protein and its function in the body.
Ubiquitin is known to form covalent bonds with proteins, marking them in the body for degradation through the ubiquitin/ATP-pathway. This process plays a vital role in the healthy turnover of proteins in the body.
When cells marked by ubiquitin bonding are not degenerated properly, the cellular homeostasis is disrupted and eventually this can result in the genesis of certain diseases.
Neurodegenerative Disorders
Isoforms of ubiquitin-1 have been found in lesions associated with some neurodegenerative disorders, such as Alzheimer and Parkinson’s disease.
Abnormally high levels are thought to decrease the malformation of amyloid precursor protein (APP), which is a trigger for Alzheimer’s disease. Abnormally low levels, on the other hand, lead to an increase in APP malformation.
Ubiquitin B changes and mutations may also lead to a lack of C-terminal glycine in some peptides, called UBB+1, which is thought to accumulate in neurodegenerative diseases.
Other Syndromes
UBE3a is usually responsible for encoding ubiquitin ligase (E3) and a disruption of this may cause a disease known as Angelman syndrome. Characteristic symptoms of this syndrome are learning and developmental disability, sleep disturbance, seizures and jerky movements like flapping of the hands.
The involvement of ubiquitin E3 may also lead to the suppression of the VHL tumor and Von Hippel-Lindau syndrome, which is a genetic disorder that involves headache and problems of balance.
Fanconi anemia is a particular type of anemia that is closely linked to an abnormality in the ubiquitin ligase complex. More than half of the genes that have been identified as responsible for the condition are associated with the role of ubiquitin.
3-M syndrome is a genetic disorder that involves significant growth retardation. It is associated with certain mutations in the E3 ubiquitin ligase proteins.
Diagnostic Techniques
In addition to playing a role as a causative factor for some diseases, ubiquitin can be used as a diagnostic marker to help identify people who are suffering from particular disease.
Ubiquitin antibodies can be used in immunohistochemistry to detect abnormal protein concentration in the body, which may be indicative of associated diseases.
Inclusion bodies, which refer to a build up of abnormal material in a cell, can be noted in several diseases, including:
- Neurofibrillary tangles (Alzheimer’s disease)
- Lewy body (Parkinson’s disease)
- Pick bodies (Pick’s disease)
- Inclusions (Huntington’s disease and motor neuron disease)
- Mallory bodies (alcoholic liver disease)
- Rosenthal fibers (astrocytes)
Using these diagnostic markers, ubiquitin can help to detect these disease and allow patients to be diagnosed and access appropriate medical therapies in a timely manner.
References
Further Reading
PARK2 duplication or microdeletion and neurological diseases