Mitochondrial DNA mutations as well as oxidative stress both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that DNA damage accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing speed. Mechanisms
Genetics
Many neurodegenerative diseases are caused by genetic mutations, most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid glutamine. A repeat of CAG results in a polyglutamine (polyQ) tract. Diseases associated with such mutations are known as trinucleotide repeat disorders.Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ studies often use a variety of animal models because there is such a clearly defined trigger – repeat expansion.
Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception. A PRKAR1A mutation has been identified in acrodysostosis with hormone resistance. Diagnosis
Treatment
There are currently no approved treatments or standardised treatment guidelines for acrodysostosis. Management of acrodysostosis typically focuses on addressing specific symptoms that occur in each individual and may include surgery, physical therapy and special education. Research
A number of transgenic mouse models have been generated that harbour genetic mutations within genes linked to the condition in humans. These mouse models exhibit phenotypes similar to that observed in Acrodysostosis in humans. Media
The actress Olivia Colman partnered with the charity Acrodysostosis Support and Research to raise awareness for the disease. She participated in a promotional video campaign in December 2020. References
External links
"Acrodysostosis: Support and Research". "Acrodysostosis: Disease Information from NORD". National Organization for Rare Disorders. Acrodysostosis at NIHs Office of Rare Diseases