Summary: Findings could help researchers hone in on new targets and treatments for Alzheimer’s and other neurodegenerative diseases.
Source: University of Plymouth.
Discovery relating to brain proteins could lead to new effective therapies for dementia and other neurodegenerative diseases.
A research team from the University of Plymouth, University of Southampton and the Alexander Fleming Biomedical Sciences Research Center, Vari, Greece, have studied two structurally-similar proteins in the adult brain and have found that they play distinct roles in the development of dementia.
Their study is published in the prestigious journal Neurobiology of Disease.
The understanding and knowledge gained from this study could lead to effective therapies for dementia and other neurodegenerative diseases.
Tau proteins stabilise microtubules in the brain and nervous system. Microtubules help form the structure of cells and other functions, such as providing the rail tracks for transport between cells.
In the brain of dementia patients, the abnormal clumping of Tau proteins have long been linked to changes in nerve cell activation and ultimately cell death. Two structurally different forms of Tau exist. The research team expressed these two forms of human Tau in nerve cells of the Drosophila (fruit fly) brain, examining their effects on nerve cell survival and activation, fly movement and memory formation.
The results show that these two proteins differ in terms of biology and pathological potential. One leads to poor communication between nerves associated with movement. The other leads to greater neurodegeneration and impairments in learning and memory.
This is important because defects in the proteins have a bearing on neurodegenerative diseases such as dementia. Designing drugs which target each form specifically should help to improve specific symptoms.
Involved in the study from the University of Plymouth is Dr Torsten Bossing. He commented: “With each new discovery like this we move one step closer to finding effective drug treatments for debilitating neurodegenerative diseases. This is an important study carried out using nerve cells from fruit flies and it has the potential over the coming years to be developed through more testing and clinical trials. We firmly believe that the answer to the question of how we treat conditions such as dementia lies at this cellular level.”
About this neuroscience research article
Funding: The study received funding from the Royal Society (Plymouth), the Wessex Medical Trust and Gerald Kerkut Trust (Southampton), and the European Social Fund and Greek National Funds (THALIS-UOA) (Vari).
Source: Andrew Gould – University of Plymouth Image Source: NeuroscienceNews.com image is credited to Dr Torsten Bossing, University of Plymouth. Original Research: Full open access research for “Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy” by Megan A. Sealey, Ergina Vourkou, Catherine M. Cowan, Torsten Bossing, Shmma Quraishe, Sofia Grammenoudi, Efthimios M.C. Skoulakis, and Amritpal Mudher in Neurobiology of Disease. Published online May 11 2017 doi:10.1016/j.nbd.2017.05.003
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]University of Plymouth “Flies Are Key to Studying the Causes of Dementia.” NeuroscienceNews. NeuroscienceNews, 19 May 2017. <https://neurosciencenews.com/dementia-flies-6729/>.[/cbtab][cbtab title=”APA”]University of Plymouth (2017, May 19). Flies Are Key to Studying the Causes of Dementia. NeuroscienceNew. Retrieved May 19, 2017 from https://neurosciencenews.com/dementia-flies-6729/[/cbtab][cbtab title=”Chicago”]University of Plymouth “Flies Are Key to Studying the Causes of Dementia.” https://neurosciencenews.com/dementia-flies-6729/ (accessed May 19, 2017).[/cbtab][/cbtabs]
Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy
Tau exists as six closely related protein isoforms in the adult human brain. These are generated from alternative splicing of a single mRNA transcript and they differ in the absence or presence of two N-terminal and three or four microtubule binding domains. Typically all six isoforms have been considered functionally similar. However, their differential involvement in particular tauopathies raises the possibility that there may be isoform-specific differences in physiological function and pathological role. To explore this, we have compared the phenotypes induced by the 0N3R and 0N4R isoforms in Drosophila. Expression of the 3R isoform causes more profound axonal transport defects and locomotor impairments, culminating in a shorter lifespan than the 4R isoform. In contrast, the 4R isoform leads to greater neurodegeneration and impairments in learning and memory. Furthermore, the phosphorylation patterns of the two isoforms are distinct, as is their ability to induce oxidative stress. These differences are not consequent to different expression levels and are suggestive of bona fide physiological differences in isoform biology and pathological potential. They may therefore explain isoform-specific mechanisms of tau-toxicity and the differential susceptibility of brain regions to different tauopathies.
“Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy” by Megan A. Sealey, Ergina Vourkou, Catherine M. Cowan, Torsten Bossing, Shmma Quraishe, Sofia Grammenoudi, Efthimios M.C. Skoulakis, and Amritpal Mudher in Neurobiology of Disease. Published online May 11 2017 doi:10.1016/j.nbd.2017.05.003