Researchers from Drexel University reversed symptoms of Alzheimer’s disease in fruit flies by restoring the balance between two epigenetic enzymes that regulate gene expression, a study shows.
Early in the progression of Alzheimer’s disease, cognitive impairment (such as difficulties with learning and memory) may be tied to the presence of elevated levels of the HDAC2 enzyme. HDAC2 helps control how genes linked to learning and memory are expressed. It appears that when HDAC2 overwhelms the enzyme it is paired with, which is called Tip60 HAT, it represses genes and leads to problems with neuroplasticity — the brain’s ability to adapt to new stimuli or recall reactions to stimuli it already encountered.
But a research team led by Priyalakshmi Panikker, a PhD student, and Felice Elefant, PhD, an associate professor, both in Drexel’s College of Arts and Sciences, performed tests in flies and found that if they added extra Tip60 HAT in the brain of flies that displayed symptoms close to Alzheimer’s disease, the balance between the enzymes could be successfully restored. When that balance came back, behaviors the team had taught the flies were able to be learned again and remembered.
“Our findings strongly support the concept of exploring the efficacy of specific Tip60 HAT activators, as well as identifying and manipulating additionally misregulated Tip60 target genes,” Elefant said.
Elefant, Panikker and their team — whose findings were published in the Journal of Neuroscience — looked at how Alzheimer’s disease affected flies early in their development, during their larval stages, to catch what might happen in Alzheimer’s well before the tell-tale symptoms arise.
“Many researchers that study Alzheimer’s disease utilize human post-mortem samples, and thus, they are not looking at what is happening during the early progression of neurodegeneration, including whether we can correctwhat is happening during these early stages ,” Elefant said.
For the study, flies were taught to associate a certain odor with sucrose — table sugar, which flies eat and is a positive reinforcement. After being exposed to the scent paired with sugar, the flies learned to move towards the scent even without the sugar present.
Flies that modeled Alzheimer’s disease showed no difference in their reaction to the smell they had earlier been condition to. This showed that their ability to learn and remember this association was negatively affected.
But once Tip60 HAT was introduced in the brain to correct the identified Tip60 HAT/HDAC2 imbalance, these flies showed a reaction time comparable to the ones without the Alzheimer’s type of condition. This indicated that they recovered their ability to learn and remember after the epigenetic balance was reintroduced.
Moreover, when researchers identified a collection of genes related to brain function that had been repressed in the flies — due to elevated HDAC2 — an introduction of increased Tip60 HAT levels in the brain restored regular function in 9 of the 11 genes tested.
The results Panikker and Elefant found were encouraging. More testing is needed, but Elefant’s goal is to find new avenues for gene therapy.
“When people age, they have a loss of memory but it’s not because there are mutations in their genes,” Elefant said. “It’s the way they’re packaged. They’re distorted. And we’re seeing non-invasive ways we might be able to prevent that early on.”
Those interested in reading the full study, “Restoring Tip60 HAT/HDAC2 balance in the neurodegenerative brain relieves epigenetic transcriptional repression and reinstates cognition,” can access it here.
The Latest on: Alzheimer’s disease
via Google News
The Latest on: Alzheimer’s disease
- Study: Many patients treated for iNPH also develop Alzheimer’s diseaseon November 15, 2019 at 4:56 am
Up to one in five patients treated for idiopathic normal pressure hydrocephalus, iNPH, also develop Alzheimer’s disease, according to a new study from the University of Eastern Finland and Kuopio ...
- Early dementia signs vs. plain old agingon November 15, 2019 at 2:00 am
Sticking your head in the sand and ignoring the warning signs of Alzheimer's disease helps no one -- certainly not the person afflicted. In fact, not everyone who shows the various Alzheimer's ...
- EastGate Biotech Expands Pipeline to Alzheimer’s Disease Using its Alternative Insulin Delivery Platformon November 14, 2019 at 4:42 pm
The initial plan is to determine the most patient-friendly and effective delivery of the company’s innovative insulin solution to treat the early onset of Alzheimer’s disease. The company is currently ...
- Plant sphingolipids promote extracellular vesicle release and alleviate amyloid-β pathologies in a mouse model of Alzheimer’s diseaseon November 14, 2019 at 3:06 am
Alzheimer’s disease (AD) is a common form of dementia with a pathology characterised by the progressive intracerebral accumulation of amyloid-β protein (Aβ). This accumulation results from impaired ...
- Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s diseaseon November 13, 2019 at 2:35 am
Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease. We further explored this unexpected observation which ...
- Alzheimers Disease Diagnostic Market Growth, Latest Trend and Forecast 2019-2026on November 12, 2019 at 11:37 pm
Nov 13, 2019 (Global QYResearch via COMTEX) -- The report on Global Alzheimers Disease Diagnostic Market is the latest addition to the huge database of Ameco Research. This research study is segmented ...
- Alzheimer’s disease is devastating | PennLive letterson November 12, 2019 at 3:59 pm
Alzheimer’s disease is devastating – not only for the more than five million Americans living with the disease, but also for the more than 16 million family and friends serving as caregivers. The ...
- Neural Stem Cells for Frontotemperal Dementia and Alzheimer's Diseaseon November 12, 2019 at 2:49 am
Alzheimer's disease (AD) is a neurodegenerative condition that is strongly linked with aging and is responsible for 60 to 70% of all dementia cases. Accounting for around 2 to 3% of AD cases, early ...
- Retinal imaging technology for early detection of Alzheimer's diseaseon November 12, 2019 at 1:35 am
Alzheimer's disease is the leading cause of dementia in the U.S., with approximately 5.4 million currently affected and an estimated 16 million by 2050. Damage to the brain from Alzheimer's disease ...
via Bing News