Редактирование: CREB1 (раздел)

==Publications==

{{medline-entry
|title=Arginine Methyltransferase [[PRMT8]] Provides Cellular Stress Tolerance in Aging Motoneurons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30054395
|abstract=Aging contributes to cellular stress and neurodegeneration. Our understanding is limited regarding the tissue-restricted mechanisms providing protection in postmitotic cells throughout life. Here, we show that spinal cord motoneurons exhibit a high abundance of asymmetric dimethyl arginines (ADMAs) and the presence of this posttranslational modification provides protection against environmental stress. We identify protein arginine methyltransferase 8 ([[PRMT8]]) as a tissue-restricted enzyme responsible for proper ADMA level in postmitotic neurons. Male [[PRMT8]] knock-out mice display decreased muscle strength with aging due to premature destabilization of neuromuscular junctions. Mechanistically, inhibition of methyltransferase activity or loss of [[PRMT8]] results in accumulation of unrepaired DNA double-stranded breaks and decrease in the cAMP response-element-binding protein 1 ([[CREB1]]) level. As a consequence, the expression of [[CREB1]]-mediated prosurvival and regeneration-associated immediate early genes is dysregulated in aging [[PRMT8]] knock-out mice. The uncovered role of [[PRMT8]] represents a novel mechanism of stress tolerance in long-lived postmitotic neurons and identifies [[PRMT8]] as a tissue-specific therapeutic target in the prevention of motoneuron degeneration.  Although most of the cells in our body have a very short lifespan, postmitotic neurons must survive for many decades. Longevity of a cell within the organism depends on its ability to properly regulate signaling pathways that counteract perturbations, such as DNA damage, oxidative stress, or protein misfolding. Here, we provide evidence that tissue-specific regulators of stress tolerance exist in postmitotic neurons. Specifically, we identify protein arginine methyltransferase 8 ([[PRMT8]]) as a cell-type-restricted arginine methyltransferase in spinal cord motoneurons (MNs). [[PRMT8]]-dependent arginine methylation is required for neuroprotection against age-related increased of cellular stress. Tissue-restricted expression and the enzymatic activity of [[PRMT8]] make it an attractive target for drug development to delay the onset of neurodegenerative disorders.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Arginine
* Cell Line
* Cyclic AMP Response Element-Binding Protein
* DNA Breaks, Double-Stranded
* DNA Damage
* DNA Repair
* Isometric Contraction
* Male
* Mice
* Mice, Knockout
* Mice, Transgenic
* Motor Neurons
* Muscle Cells
* Neuromuscular Junction
* Protein-Arginine N-Methyltransferases
* RNA Interference
* RNA, Small Interfering
* Recombinant Fusion Proteins
* Reflex, Abnormal
* Rotarod Performance Test
* Spinal Cord
|keywords=* ADMA
* CREB1
* PRMT8
* aging
* motoneuron
* neurodegeneration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113905
}}