Antibiotics Could be Promising Treatment for Form of Dementia
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Antibiotics could be promising treatment for form of dementia:
Frontotemporal dementia is the second-most common dementia after Alzheimer's disease and the most common type of early onset dementia. It typically begins between ages 40 and 65 and affects the frontal and temporal lobes of the brain, which leads to behavior changes, difficulty speaking and writing, and memory deterioration.
A subgroup of patients with frontotemporal dementia have a specific genetic mutation that prevents brain cells from making a protein called progranulin. Although progranulin is not widely understood, its absence is linked to the disease.
A group led by Haining Zhu, a professor in UK's Department of Molecular and Cellular Biochemistry, discovered that after aminoglycoside antibiotics were added to neuronal cells with this mutation, the cells started making the full-length progranulin protein by skipping the mutation.
"These patients' brain cells have a mutation that prevents progranulin from being made. The team found that by adding a small antibiotic molecule to the cells, they could 'trick' the cellular machinery into making it," said Matthew Gentry, a co-author of the study and the Antonio S. Turco Endowed Professor in the Department of Molecular and Cellular Biochemistry.
The researchers found two specific aminoglycoside antibiotics -- Gentamicin and G418 -- were both effective in fixing the mutation and making the functional progranulin protein. After adding Gentamicin or G418 molecules to the affected cells, the progranulin protein level was recovered up to about 50 to 60%.
Journal Reference:
Lisha Kuang, Kei Hashimoto, Eric J Huang, Matthew S Gentry, Haining Zhu. Frontotemporal dementia nonsense mutation of progranulin rescued by aminoglycosides. Human Molecular Genetics, 2020; DOI: 10.1093/hmg/ddz280
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