Related Experiment Video

Updated: Jun 8, 2025

SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
07:39

SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs

Published on: June 28, 2019

23.8K

BRD7 regulates cellular senescence and apoptosis in ALS by modulating p21 expression and p53 mitochondrial

Xingli Tan1, Xiaoli Su1, Ying Wang1

  • 1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China.

Neuroscience
|November 7, 2024
PubMed

Insights

Bromodomain-containing protein 7 (BRD7) upregulation drives cellular senescence and apoptosis in amyotrophic lateral sclerosis (ALS) motor neurons. Downregulating BRD7 protects motor neurons by inhibiting senescence and apoptosis pathways.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • Cellular senescence contributes to neurodegenerative disease progression.
  • Amyotrophic lateral sclerosis (ALS) motor neurons display senescence-like changes.
  • The role of BRD7, a senescence regulator, in ALS is not well understood.

Purpose of the Study:

  • To investigate the function and mechanisms of BRD7 in ALS.
  • To determine if BRD7 influences cellular senescence and apoptosis in ALS motor neurons.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) for RNA analysis.
  • Immunofluorescence and Western blot for protein level assessment.
  • TUNEL staining for apoptosis detection.
  • In vitro cell transfection and beta-galactosidase activity assays.

Main Results:

  • ALS motor neurons showed increased p53, p21, and beta-galactosidase activity, with reduced lamin B1, indicating senescence.
  • BRD7 expression was elevated in ALS, inducing senescence and apoptosis.
  • BRD7 downregulation reduced senescence by inhibiting p21 and decreased apoptosis by preventing p53 mitochondrial translocation.

Conclusions:

  • BRD7 plays a critical role in ALS motor neuron survival.
  • Targeting BRD7 can mitigate cellular senescence and apoptosis in ALS.
  • BRD7 inhibition offers a potential therapeutic strategy for ALS.
Keywords:
Amyotrophic lateral sclerosisApoptosisBRD7Cellular senescence

More Related Videos

Induction and Validation of Cellular Senescence in Primary Human Cells08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

16.7K
A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.1K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K