More Hope for Drug-Based Alzheimer Treatments
upstart writes:
mRNA quality control identified as novel drug target for Alzheimer's and related dementias:
Alzheimer's disease and similar disorders are often marked by the presence of pathological forms of proteins that cause neurons to die. Besides the amyloid beta proteins, which have received a lot of attention, there are also the tau proteins. Researchers from The University of Texas Health Science Center at San Antonio discovered a new mechanism whereby pathological forms of tau proteins cause cell death, which they believe can be treated with drugs.
These proteins are created from messenger RNA (mRNA) that carry nonsense mutations. Clearing out these aberrant mRNAs occurs through a process called nonsense-mediated mRNA decay (NMD). The researchers noticed that pathological tau protein buildup was associated with disruptions in the NMD process. Instead of trying to figure out how to clear out the proteins, they think they can attack the cause of the NMD disruptions.
"We are focusing on how cells clear faulty RNAs, and how this RNA quality control mechanism goes awry in disease. If these types of RNAs accumulate in a cell and are translated into proteins, bad things can happen," said senior author Bess Frost, PhD, Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders at UT Health San Antonio.
[...] Treatments for Alzheimer's disease and other tauopathies have failed in part because they focused on clearing tau protein or another protein called amyloid beta. Amyloid beta plaques and tau tangles are classic hallmarks of Alzheimer's.
Journal Reference:
Gabrielle Zuniga, Simon Levy, Paulino Ramirez, Jasmine De Mange, Elias Gonzalez, Maria Gamez and Bess Frost, Tau-induced deficits in nonsense-mediated mRNA decay contribute to neurodegeneration, Alzheimer's & Dementia, 2022
DOI: 10.1002/alz.12653
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