Key protein identified for brain stem cell longevity

Key protein identified for brain stem cell longevity

Summary: INSR, a protein essential for insulin activity, plays an essential role in the longevity of stem cells. Additionally, inactivation of INSR in glioblastoma brain cancer stem cells inhibits the growth of primitive tumor-forming cells.

Source: Rutgers

A receptor that was first identified as necessary for insulin action, which is also located on neural stem cells found deep in the brains of mice, is essential for brain stem cell longevity, according to a researcher. Rutgers study, a finding that has important implications for brain health and future therapies for brain disorders.

The study, published in the journal Stem Cell Reportsidentifies a specific protein known as the insulin receptor (INSR), which is abundant on neural stem cells that reside in the subventricular area of ​​the brain.

During development, neural stem cells give rise to the entire nervous system and persist into adulthood. Over the course of life, these neural stem cells produce new neurons and non-neuronal cells that maintain brain infrastructure and function.

Separately, scientists have made another discovery when examining brain tumors: INSR plays a crucial role in maintaining and sustaining a population of specialized brain cancer cells called glioblastoma stem cells (GBMs). When they inactivated the INSR in GBM stem cells, they inhibited the growth of these primitive tumor-forming cells.

“It is important to understand the molecular mechanisms that are essential for the growth and sustenance of brain stem cells in normal and abnormal growth states,” said study author Steven Levison, professor of neuroscience at Department of Pharmacology, Physiology and Neurosciences and Director. from the Regenerative Neurobiology Laboratory at Rutgers New Jersey Medical School.

“Understanding the signals that regulate these primitive cells could one day lead to new therapies for brain disorders.”

Many neurodegenerative disorders, such as multiple sclerosis, Parkinson’s disease and Alzheimer’s disease, are linked to the destruction of brain cells, said co-author Teresa Wood, professor emeritus and endowed chair holder. the Rena Warshow Professorship in Multiple Sclerosis in the Department of Pharmacology, Physiology, and Neurosciences at Rutgers New Jersey Medical School.

“If we could influence how brain stem cells work, we could use this knowledge to replace diseased or dead brain cells with living ones, which would advance the treatment of neurological disease and brain injury,” said Wood, who also teaches and conducts research at the Cancer Institute of New Jersey.

Cellular receptors such as INSR are protein molecules that reside on the surface of cells. Substances, natural or man-made, that open a receptor’s “lock” can cause a cell to divide, differentiate, or die.

By identifying which receptors perform these functions on specific cell types and understanding their structures and functions, scientists can design substances that act as keys for the receptors, to turn them on or off.

Previous studies by this research team had shown that a certain “key”, the signaling protein known as insulin-like growth factor (IGF-II), was needed to maintain neural stem cells at two places in the adult brain. which house these primitive cells.

This shows a drawing of a brain with a hand underneath
Adult neurogenesis – the idea that new cells are produced in the adult brain – has been a booming field of scientific research since the late 1990s, when researchers confirmed what was only a theory in laboratory studies of the brains of humans, primates and birds. Image is in public domain

In the current experiment, the scientists sought to identify the receptor. To do this, they used genetic tools allowing them to both delete the INSR and introduce a fluorescent protein in order to follow the neural stem cells and the cells they generate.

They found that the number of neural stem cells in the subventricular area of ​​the brains of mice lacking INSR plummeted.

Adult neurogenesis – the idea that new cells are produced in the adult brain – has been a booming field of scientific research since the late 1990s, when researchers confirmed what was only a theory in laboratory studies of the brains of humans, primates and birds. Adult neural stem cells are stem cells that can self-renew and produce new neurons and the brain’s supporting cells, oligodendrocytes and astrocytes.

“Given the widespread interest in stem cells as well as the interest in whether alterations in adult stem cells could contribute to cancer, our research results should be interesting,” Levison said.

About this genetic research news

Author: Press office
Source: Rutgers
Contact: Press office – Rutgers
Picture: Image is in public domain

Original research: Free access.
“Adult mouse neural stem cells from the subventricular zone require an insulin receptor for self-renewal” by Shravanthi Chidambaram et al. Stem Cell Reports


Abstract

See also

This is a cartoon of a man holding a heart and a brain

Adult mouse neural stem cells from the subventricular zone need an insulin receptor to self-renew

Strong points

  • Insulin receptor (INSR) is essential for self-renewal of adult SVZ neural stem cells
  • INSR suppression causes hyposmia with increased olfactory bulb neurogenesis
  • Hippocampal stem cells (and associated behaviors) do not require INSR
  • Glioblastomas overexpress the components of the INSR pathway necessary for the growth of the tumor sphere

Summary

The insulin receptor (INSR) is an evolutionarily conserved signaling protein that regulates cell development and metabolism. INSR signaling promotes neurogenesis in Drosophila; however, a specific role of INSR in maintaining adult neural stem cells (NSCs) in mammals has not been studied.

We show that the conditional deletion of Insert The gene in adult mouse NSCs reduces subventricular zone NSCs by approximately 70%, with a corresponding increase in progenitors.

Insert suppression also produced hyposmia caused by aberrant neurogenesis of the olfactory bulb. Interestingly, hippocampal neurogenesis and hippocampal-dependent behaviors were not disrupted.

Highly aggressive proneural and mesenchymal glioblastomas had elevated INSR/insulin-like growth factor (IGF) pathway gene expression, and isolated glioma stem cells had an abnormally high ratio of INSR:IGF type 1 receptors.

Besides, INSR knockdown inhibited the growth of the GBM tumorsphere. Taken together, these data demonstrate that INSR is essential for a subset of normal NSCs, as well as for brain tumor stem cell self-renewal.

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