ISLAMABAD, January 24 (Online): Alzheimer\u2019s disease is the most commonTrusted Source form of dementia and is estimated to affect about 32 million peopleTrusted Source worldwide.
\nWhile scientists are still unclear as to the true cause of Alzheimer\u2019s disease, they do know a loss of neuronsTrusted Source in the brain plays an important role.<\/p>\n
Now, in a new study published in the journal Nature CommunicationsTrusted Source, researchers from Northwestern University have found a possible new cause of neuron death in Alzheimer\u2019s through toxic RNATrusted Source strands.
\nWhat causes brain cell loss in Alzheimer\u2019s disease?
\nMedical News Today spoke with Dr. Marcus Peter, Ph.D., the Tom D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine and senior author of this study. Dr. Peter told MNT that he and his team decided to focus on what causes brain cell loss in Alzheimer\u2019s disease after discovering a novel and powerful anti-cancer mechanismTrusted Source a few years ago.<\/p>\n
\u201cWe hypothesized that this mechanism, while powerful in killing cancer cells, may also under certain circumstances kill normal cells,\u201d Dr. Peter explained. \u201cWe were looking for diseases that are characterized by cell loss \u2014 such as neurodegenerative diseasesTrusted Source \u2014 and we predicted that patients suffering from such diseases would have lower cancer rates.\u201d
\n\u201cWe found it in Alzheimer\u2019s disease as it has been described multiple times that Alzheimer\u2019s disease patients have less cancerTrusted Source. So we tested whether our original anti-cancer kill code was contributing to Alzheimer\u2019s disease pathology and found ample evidence for that.\u201d<\/p>\n
\u2013 Dr. Peter
\nCould RNA be contributing to brain cell death?
\nFor this study, Dr. Peter and his team analyzed the brains of several sources, including mouse models of Alzheimer\u2019s disease, stem cell-derived neurons for both people with and without Alzheimer\u2019s, and older adults over age 80 with memory capacity equivalent to individuals 50 to 60 years old.
\nDuring the study, researchers focused on RNA and how it might contribute to brain cell death.
\nAccording to Dr. Peter, every person has different classes of RNA in all their cells, and two of them are most relevant to this study\u2019s findings.<\/p>\n
\u201cThe first class is long RNAs \u2014 so-called messenger (m)RNAsTrusted Source \u2014 that code for the proteins that make all our cells function,\u201d he explained. \u201cThey are being converted into proteins. mRNAs are hundreds or thousands of nucleotidesTrusted Source long.\u201d
\nThe second class is short (s)RNAsTrusted Source, which Dr. Peter said are 19-22 nucleotides in length.
\n\u201cThis class acts by suppressing the activity of the long mRNAs,\u201d he added. \u201cThat results in the block of converting the long mRNAs into proteins.\u201d<\/p>\n
How a \u2018kill code\u2019 can affect survival of healthy neurons
\nDuring previous research, Dr. Peter and his team found a code embedded in the short RNAs that are just six nucleotides long.
\n\u201cWhen this sequence is present at a certain position of these sRNAs, they kill all cells,\u201d he detailed. \u201cWe called the short sequence the \u2018kill code.\u2019 Cells die because sRNAs that carry the code selectively suppress mRNAs that code for proteins that (are) critical for the survival of all cells.\u201d
\n\u201cJust like we have organs we cannot live without (i.e., the heart), cells have proteins they cannot live without. sRNAs that carry the kill code suppress such proteins and cells die.
\nInterestingly, the sRNAs that carry the kill code can be balanced out by sRNAs that do not carry the kill code. They act as protectors when present (in) large quantities.\u201d<\/p>\n
\u2013 Dr. Peter
\nDr. Peter said their model now predicts that in any normal cell, there are enough protective sRNAs to balance out the toxic ones.
\n\u201cBrain cells are also protected by these nontoxic sRNA, but are particularly susceptible to the toxic sRNAs,\u201d he continued. \u201cWe now show that with age, the amount of protective sRNAs goes down and that of toxic ones goes up. That should happen (to) all of us.\u201d
\n\u201cHowever, when there are higher amounts of toxic RNAs present then at a certain age the protection will not be sufficient enough anymore, and pathology can emerge.\u201d Dr. Peter added. \u201cThe toxic sRNAs can now kill the neurons.\u201d<\/p>\n
More research needed on beta-amyloid and tau protein buildups
\nFor many years, the common consensus among researchers is that clumps of beta-amyloidTrusted Source proteins called plaques and tauTrusted Source proteins called tangles within the brain are the main cause of Alzheimer\u2019s disease.
\n\u201cThese proteins are certainly involved and important,\u201d Dr. Peter said. \u201cHowever, it could never be shown how exactly they result in the death of neurons. Our work now provides a new model for how that occurs. The toxic sRNAs are downstream of these two proteins. We believe that they are the executioners.\u201d<\/p>\n
When asked if these new RNA-based findings might result in new treatments for Alzheimer\u2019s disease, Dr. Peter said this new avenue still needs to be explored:
\n\u201cIn our paper, we show that stabilizing or increasing the amount of protective sRNAs or inhibiting the toxic sRNAs can rescue cells from cell death. This provides new avenues for drug development to treat AD and potentially other neurodegenerative diseases.
\n\u201c(Research next steps include) testing our concept in more animal models and in Alzheimer\u2019s disease patients derived neurons and postmortem brain tissues,\u201d Dr. Peter continued. \u201cThen screening and testing for drugs that either increase the level of the protective sRNAs or reduce the activity of the toxic ones. There are concepts and ideas that need to be and can be tested now.\u201d<\/p>\n
Hope for new treatments for neurodegenerative diseases
\nAfter reviewing this study, Dr. Karen D. Sullivan, a board certified neuropsychologist, owner of I CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, NC, told MNT that the insights gained from this study give us a better understanding of both what goes very wrong in the aging brain via Alzheimer\u2019s disease and what goes very right in the aging brain with SuperAgers.<\/p>\n
\u201cIt also gives hope for a novel intervention pathway to stop or slow down this devastating neurodegenerative disease,\u201d Dr. Sullivan continued. \u201cOver 90% of current Alzheimer\u2019s disease research efforts focus on the compounds amyloid and tau. This study suggests that another disease process, RNA, may be a target for future treatments.\u201d
\nMNT also spoke about the study with Dr. Clifford Segil, a neurologist at Providence Saint John\u2019s Health Center in Santa Monica, CA.
\nDr. Segil said he is cautiously optimistic that RNA-based therapiesTrusted Source that are being introduced for many diseases will have good clinical neurological applications.<\/p>\n
\u201cThis study clearly showed that there is neurotoxicity related (to) the genes that they looked at,\u201d he continued. \u201cThe study is also trying to state that there (are) neuroprotective benefits from these types of medications and other disease states.\u201d
\n\u201cI\u2019m hopeful that something like an mRNA-based therapy can be neuroprotective in humans, given the right research in other animals working up to humans one day,\u201d Dr. Segil added. \u201cI think it\u2019s optimistically cautious.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
ISLAMABAD, January 24 (Online): Alzheimer\u2019s disease is the most commonTrusted Source form of dementia and is estimated to affect about 32 million peopleTrusted Source worldwide. While scientists are still unclear as to the true cause of Alzheimer\u2019s disease, they do know a loss of neuronsTrusted […]<\/p>\n
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