# The Heme Oxygenase/Biliverdin Reductase System as a Therapeutic Target to Counteract Cellular Senescence in Alzheimer’s Disease

## TL;DR

This paper explores how the HO/BVR system could be a new treatment target for Alzheimer’s disease by addressing cellular senescence and neurodegeneration.

## Contribution

The paper highlights the potential of the HO/BVR system to counteract cellular senescence in Alzheimer’s disease, a novel therapeutic angle.

## Key findings

- Cellular senescence contributes to Alzheimer’s disease through neurotoxic effects and inflammation.
- The HO/BVR system is a promising but underexplored target for modulating cellular senescence in AD.
- Xenobiotics activating HO/BVR show neuroprotective effects, but their direct link to AD senescence remains unproven.

## Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder involving free radical overload, neuroinflammation, and a deranged cell stress response. In particular, the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system, a key component of the brain stress response, is currently regarded as a promising therapeutic approach for AD. Cellular senescence, defined as a process of cell cycle arrest due to oxidative stress, DNA damage, mitochondrial dysfunction, and oncogene activation, has been identified as a pivotal factor in the development of AD. A mounting body of research has demonstrated that the accumulation of senescent cells in the brain can lead to a variety of neurotoxic effects, including synaptic dysfunction, the destruction of the blood–brain barrier, and impaired remyelination. Finally, the release of proinflammatory molecules by senescent cells further exacerbates neurodegeneration. A considerable number of xenobiotics, with well-documented neuroprotective effects through the activation of the HO/BVR system, have been shown to modulate pathways involved in cellular senescence outside the brain. Unfortunately, a direct link between HO/BVR and cellular senescence in AD is yet to be established. This compelling evidence should motivate basic and clinical researchers to address such a significant gap in knowledge and conduct novel studies in this field.