{"id":464569,"date":"2025-12-22T15:06:23","date_gmt":"2025-12-22T15:06:23","guid":{"rendered":"https:\/\/www.europesays.com\/us\/464569\/"},"modified":"2025-12-22T15:06:23","modified_gmt":"2025-12-22T15:06:23","slug":"ut-southwestern-research-findings-on-inflammatory-cell-death-could-lead-to-new-treatments-for-sepsis-crohns-alzheimers-als-and-cancer-dallas-innovates","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/464569\/","title":{"rendered":"UT Southwestern Research Findings on Inflammatory Cell\u00a0Death Could Lead to New Treatments for Sepsis, Crohn\u2019s, Alzheimer\u2019s, ALS, and Cancer \u00bb Dallas Innovates"},"content":{"rendered":"

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Ayaz Najafov, Ph.D., led a UT Southwestern study that identified the protein responsible for rupturing cell membranes during necroptotic cell death. [Composite: DI Studio, source images, UTSW]<\/p>\n

Researchers at UT Southwestern Medical Center have identified a protein that causes human cell membranes to burst during necroptosis\u2014a form of programmed cell death. <\/strong><\/p>\n

The discovery could lead to new treatments for severe infections, inflammatory diseases, neurodegeneration, and cancer\u2014including conditions such as Crohn\u2019s disease, Alzheimer\u2019s, ALS, and several tumor types.<\/p>\n

Research findings, published<\/a> in Nature, identify what study leader Ayaz Najafov describes as \u201ca previously unknown, druggable control point in inflammatory cell death.\u201d <\/p>\n

Najafov, an assistant professor of internal medicine at UT Southwestern, said the protein\u2014known as SIGLEC12\u2014acts as \u201ca human-specific mediator of necroptotic membrane rupture.\u201d<\/p>\n

Why it matters<\/p>\n

Programmed cell death helps the body clear out old, damaged, or infected cells, according to Najafov, who also works in the Cellular Networks in Cancer Research Program within the Harold C. Simmons Comprehensive Cancer Center.<\/p>\n

But necroptosis\u2014a specific subtype\u2014can become harmful when inflammation triggered by infection or chronic disease pushes the process into overdrive.<\/p>\n

As Najafov explained in a UT Southwestern announcement, necroptosis ends with cell membranes rupturing, releasing distress signals that draw immune cells to clear debris and fight microbes.<\/p>\n

Scientists had already identified proteins that rupture membranes in other cell-death pathways\u2014apoptosis, pyroptosis, and ferroptosis\u2014pointing to a protein called NINJ1, he noted. But NINJ1 doesn\u2019t appear to play a role in necroptosis, leaving a missing link in understanding how this specific process ends.<\/p>\n

\u201cAlthough previous studies have identified the preceding steps in the necroptosis molecular cascade,\u201d the UTSW announcement said, \u201cnone had discovered a protein analogous to NINJ1 in this process.\u201d<\/p>\n

How UTSW researchers found it<\/p>\n

Najafov\u2019s team used CRISPR gene editing to knock out individual genes in human cells engineered to activate MLKL, which is the last known protein in the necroptosis cascade. Most cells underwent necroptosis and ruptured, except those in which CRISPR had disabled the gene that codes for SIGLEC12, a protein with parts \u201cstrikingly similar to NINJ1.\u201d<\/p>\n

When researchers pushed SIGLEC12-deficient cells to undergo necroptosis, their membranes ballooned but didn\u2019t break. Producing extra SIGLEC12 didn\u2019t trigger rupture either.<\/p>\n

The team discovered that a protein, TMPRSS4, cleaves a portion of SIGLEC12, which appears to be the key activation step. Experiments using only the \u201ccleaved\u201d form of SIGLEC12 showed it was enough to cause membranes to burst, UTSW said.<\/p>\n

A cancer connection<\/p>\n

Cells from many cancer types are less likely than healthy cells to undergo necroptosis, a trait thought to help them survive and grow, the researchers noted.<\/p>\n

Najafov and his colleagues found that many cancers carry SIGLEC12 mutations that prevent TMPRSS4 from cleaving the protein, blocking its function. They also identified similar mutations in the general population. According to Najafov, they could influence a person\u2019s vulnerability to infections or inflammatory disease.<\/p>\n

What\u2019s next<\/p>\n

Drugs targeting SIGLEC12 or TMPRSS4 could eventually be used to prevent necroptosis and treat conditions where it plays a central role, Najafov said.<\/p>\n

First author Hyunjin Noh, a postdoctoral researcher, and graduate student researcher Zeena Hashem also contributed to the study. The work was funded by the National Institute of General Medical Sciences and a National Cancer Institute Cancer Center Support Grant.<\/p>\n

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