How a protein controls the production of nerve cells in the brain

Date:
February 15, 2022
Source:
University of Cologne
Summary:
Researchers have discovered that the protein YME1L regulates
the production of new nerve cells and the maintenance of neural
stem cells in the adult brain. This holds great potential for
regenerative treatments after brain injuries and other diseases.



FULL STORY ==========================================================================
By investigating changes in the metabolic profile of neural stem cells,
a research team led by Professor Dr. Matteo Bergami from the CECAD
Cluster of Excellence for Aging Research at the University of Cologne discovered that the protein YME1L is essential in coordinating the
shift between cellular proliferation (cell division) and quiescence
(a resting state). The protein YME1L is responsible for balancing the conversion of the brain's neural stem cells, which are limited in number
and cannot be produced again, into neurons.

Defects in the functioning of this protein can lead to a premature
conversion of neural stem cells into specialized cells, and hence impair
neural regeneration in the long term. The article 'Metabolic control of
adult neural stem cell self-renewal by the mitochondrial protease YME1L'
has been published in Cell Reports.


========================================================================== Neural stem cells are maintained in only a few regions of the adult
mammalian brain, where they sustain the production of new neurons
throughout life.

Understanding how neural stem cell activity is regulated and maintained
in these regions has critical implications for regenerative approaches following brain trauma and disease. Mutations in YME1L have also been
linked to brain disorders and intellectual disability in human patients.

YME1L is a protease (an enzyme which cleaves other proteins) localized in mitochondria, the powerhouses of the cells. As for other mitochondrial proteases, YME1L plays an important role in the quality control of
proteins within mitochondria. By analysing the level of those proteins
known to be targeted by YME1L, the scientists now found that the enzymatic activity of YME1L precisely reflects different metabolic states in neural
stem cells.

Higher YME1L activity marks a quiescent (dormant) state while lower
YME1L activity matches with a proliferative state.

This balance in YME1L activity is required to maintain the stemness
properties of neural stem cells, as impairments in YME1L function force
cells to exit their status of stem cells and prematurely specialize
into different types of nerve cells, leading to the overall loss of stem
cells from brain tissue.

Ultimately, this stem cell loss has a major impact on the long-term
neurogenic capacity of the brain, as no further neurons can be produced.

'Our results show that the activity of a single mitochondrial protease
can significantly affect the fate of neural stem cells and the production
rate of new nerve cells. These findings not only reveal a new layer
of regulation in the biology of neural stem cells but may also have
important implications for patients bearing mutated YME1L,' Bergami said.

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may be edited for style and length.


========================================================================== Journal Reference:
1. Gulzar A. Wani, Hans-Georg Sprenger, Kristiano Ndoci, Srikanth
Chandragiri, Richard James Acton, De'sire'e Schatton, Sandra
M.V. Kochan, Vignesh Sakthivelu, Milica Jevtic, Jens M. Seeger,
Stefan Mu"ller, Patrick Giavalisco, Elena I. Rugarli, Elisa Motori,
Thomas Langer, Matteo Bergami. Metabolic control of adult neural
stem cell self-renewal by the mitochondrial protease YME1L. Cell
Reports, 2022; 38 (7): 110370 DOI: 10.1016/j.celrep.2022.110370 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220215113429.htm

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