{"id":13852,"date":"2024-10-31T15:09:31","date_gmt":"2024-10-31T19:09:31","guid":{"rendered":"https:\/\/www.med.unc.edu\/cellbiophysio\/?p=13852"},"modified":"2024-11-04T15:33:33","modified_gmt":"2024-11-04T20:33:33","slug":"neuronal-survival-from-the-brink-of-death","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/cellbiophysio\/neuronal-survival-from-the-brink-of-death\/","title":{"rendered":"Neuronal survival: from the brink of death"},"content":{"rendered":"

Neurons are among the few cells that can halt cell death and recover from apoptosis. Now scientists know why.<\/em><\/span><\/p>\n

\n

\u201cNeurons can reverse their decision to die from a point that\u2019s considered impossible in most other cells,\u201d said Mohanish Deshmukh<\/a>, a neuroscientist in the Department of Cell Biology and Physiology. In a recent study<\/a> published in Cell Death & Differentiation<\/em>, Keeley Spiess, a graduate student in Deshmukh\u2019s lab found that even when neurons receive a persistent signal to die, they execute the steps of the apoptotic pathway transiently. This means they are always ready to reverse previously executed apoptotic steps for self-preservation.<\/p>\n

The extraordinary ability of neurons to survive is not a surprise. Humans are born with most of the neurons they will ever have, which means that our neurons must last our entire lives for our brains to function properly. However, how neurons withstand environmental assaults, such as stress, and DNA damage to return from the brink of death was not known, until now.<\/p>\n

\"This
Spiess used fluorescent staining to identify p-c-Jun in neurons undergoing apoptosis. In this image, green indicates p-c-Jun, blue indicates cell nuclei, and red indicates alpha tubulin, a cytoskeletal protein.<\/figcaption><\/figure>\n

In their recent paper, Spiess\u00a0and Deshmukh asked if the molecular steps in the apoptotic pathway resulted in permanent changes, in which case neurons would have the herculean task of undoing numerous molecular steps to stop death, or if the molecular changes that happened during apoptosis were more transient. To activate apoptosis in neurons they removed nerve growth factor (NGF) and closely examined the molecular changes at each step in the apoptotic pathway.<\/p>\n

During the first 24-48 hours after receiving an apoptotic signal, cells phosphorylate c-Jun, a transcription regulator, which activates a family of proteins called the BH3 proteins. These proteins then bind to BAX proteins in the cytoplasm. Conformationally changed BAX proteins then attach to mitochondrial surfaces, where they bore holes into mitochondrial membranes that allow cytochrome c to enter the cytoplasm and activate caspases that then begin the process of degrading cells. Once cell degradation happens, there\u2019s no turning back, but Spiess and Deshmukh found that every step up to that point is reversible.<\/p>\n

\u201cWhat people expected is that all those steps stay \u2014 c-Jun stays phosphorylated, BH3 proteins stay activated, etc. \u2014 and the game\u2019s over. It turns out in neurons, it\u2019s more like a relay, where one step tells the other to go ahead while it resets itself in case the neuron changes its mind,\u201d said Deshmukh. A neuron can even stop cell death after BAX has poked a few holes in mitochondrial membranes. BAX does its job of releasing cytochrome c and then stops. It doesn\u2019t stay bound to the mitochondria causing persistent pores, even though the apoptotic signal of depleted NGF is still present.<\/p>\n

Spiess and Deshmukh found that to fully halt cell death and recover from initiating the apoptotic pathway after replenishing NGF, neurons need a protein called BCL-xL. BCL-xL was previously found by other research teams to be needed for preventing cell death in cancer cells, which hints that cancer cells may be able to recover from cell death in a similar manner as neurons. These findings may also provide insights into the molecular survival mechanisms of other post-mitotic cells such as cardiomyocytes that persist throughout an organism\u2019s lifespan.<\/p>\n

For Deshmukh\u2019s research team though, these research findings contribute to a different, larger research goal of better understanding neurodegeneration and the healthy adult brain. \u201c[Neuroscientists] have been studying how neurons die during injury and disease for the last 25 years. We\u2019re much more impressed with the ability of healthy neurons to survive,\u201d said Deshmukh. \u201cOur approach to tackling neurodegeneration is very different from other labs that focus on what goes wrong in the degenerating brain. We\u2019re interested in what goes right in the healthy adult brain. What do healthy neurons do to survive long term and can we utilize that knowledge to fight neurodegeneration?\u201d<\/p>\n

Reference<\/strong><\/p>\n

Spiess, K. et al<\/em>. Apoptosis signaling is activated as a transient plus in neurons<\/a>. Cell Death & Differentiation <\/em>(2024).<\/p>\n

Written by Tiffany Garbutt, PhD<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Neurons are among the few cells that can halt cell death and recover from apoptosis. Now scientists know why. \u201cNeurons can reverse their decision to die from a point that\u2019s considered impossible in most other cells,\u201d said Mohanish Deshmukh, a neuroscientist in the Department of Cell Biology and Physiology. In a recent study published in … Read more<\/a><\/p>\n","protected":false},"author":77299,"featured_media":13861,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[52,2],"tags":[83,82,84,75],"featured-item":[],"class_list":["post-13852","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-featured-news","category-news","tag-apoptosis","tag-cell-death","tag-neurons","tag-neuroscience","odd"],"acf":[],"yoast_head":"\nNeuronal survival: from the brink of death - Department of Cell Biology and Physiology<\/title>\n<meta name=\"description\" content=\"Neurons are among the few cells that can halt cell death and recover from apoptosis. 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