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Mapping microproteins in the brain might help to understand, and treat, Alzheimer\u2019s disease.Credit: Zephyr\/SPL<\/p>\n
More than 1,000 previously overlooked \u2018microproteins\u2019 have been found in samples of human brain tissue, providing researchers with the most comprehensive database yet to study these hidden molecules inside the brain. Dozens of the tiny proteins showed altered expression in people with Alzheimer\u2019s disease, which could pave the way to unlocking new mechanisms of ageing and neurodegeneration.<\/p>\n
Microproteins are small proteins with fewer than 150 amino acids and are notoriously difficult to detect with standard gene and protein sequencing techniques. In a study published in Nature Aging on 14 September1<\/a>, researchers combined several methods to pinpoint the tiny molecules in post-mortem samples of the dorsolateral prefrontal cortex \u2014 a region of the brain involved in cognitive control \u2014 from people with and without Alzheimer\u2019s disease.<\/p>\n The team identified more than 4,300 microproteins, creating the largest atlas of microproteins in Alzheimer\u2019s disease made so far.<\/p>\n \u201cWe might be actually missing a whole layer of biology by overlooking these microproteins,\u201d says Bahareh Ajami, a neuroimunologist at Cedars-Sinai Medical Center in Los Angeles, California.<\/p>\n \u201cAlzheimer\u2019s disease is a proteinopathy [wherein] the pathology is in part due to the proteins that have misfolded or accumulated and evoked a toxic response,\u201d says study co-author Brendan Miller, a neuroscientist at the Salk Institute for Biological Studies in San Diego, California. \u201cIt should be somewhat urgent to understand the full proteome,\u201d including microproteins, he adds.<\/p>\n A new detection tool<\/p>\n Microproteins are sometimes referred to<\/a> as \u201cthe dark matter of the genome\u201d, says Miller. Because of their short length, the standard method to identify the protein content of cells, known as mass spectrometry, often fails to detect them.<\/p>\n Some microproteins are made by parts of the genome that were thought to be non-coding and unable to produce proteins. But others are made from coding genes that also produce large, known proteins, explains Miller. This has made it difficult to find microproteins using conventional RNA-sequencing techniques.<\/p>\n
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