Researchers in the US have uncovered a previously-unknown biological process which could lead to new treatments for Alzheimer’s and other neurodegenerative diseases.
The team at Northwestern Medicine identified short strands of toxic RNAs that contribute to brain cell death and DNA damage in Alzheimer’s and aged brains.
Short strands of protective RNAs are decreased during ageing, the research reveals, which may allow Alzheimer’s to develop.
The study also found that older people with a superior memory capacity (known as SuperAgers) have higher amounts of protective short RNA strands in their brain cells.
SuperAgers are individuals aged 80 and above with a memory capacity of individuals 20 to 30 years younger.
Corresponding study author Marcus Peter is the Tom D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine.
He said. “Nobody has ever connected the activities of RNAs to Alzheimer’s.
“We found that in ageing brain cells, the balance between toxic and protective sRNAs shifts toward toxic ones.”
The new discovery may have relevance beyond Alzheimer’s.
Peter said: “Our data provide a new explanation for why, in almost all neurodegenerative diseases, affected individuals have decades of symptom free life and then the disease starts to set in gradually as cells lose their protection with age.”
All of our gene information is stored in form of DNA in the nucleus of every cell.
To turn the gene information into the building blocks of life, DNA needs to be converted into RNA which is used by cell machinery to produce proteins.
RNA is essential for the majority of our biological functions.
As well as these long coding RNAs, there are large numbers of short RNAs (sRNAs), which do not code for proteins.
These have other critical functions in the cell.
One class of such sRNAs suppresses long coding RNAs through RNA interference that results in the silencing of the proteins that the long RNAs code for.
The researchers have now identified very short sequences present in some of these sRNAs that when present can kill cells by blocking production of proteins required for cells to survive resulting in cell death.
The data suggest that these toxic sRNAs are involved in the death of neurons which contributes to the development of Alzheimer’s disease.
Peter said: “The overwhelming investment in Alzheimer’s drug discovery has been focused on two mechanisms: reducing amyloid plaque load in the brain — which is the hallmark of Alzheimer’s diagnosis and 70 to 80 per cent of the effort — and preventing tau phosphorylation or tangles.
“However, treatments aimed at reducing amyloid plaques have not yet resulted in an effective treatment that is well tolerated.
“Our data support the idea that stabilising or increasing the amount of protective short RNAs in the brain could be an entirely new approach to halt or delay Alzheimer’s or neurodegeneration in general.”