Enzyme strands intertwined in brain.

Unlocking Alzheimer's: Can This Enzyme Hold the Key to Prevention?

Beau Callahan in Health & Wellness August 2025 • 4 min read.

"New research suggests a vital enzyme, reduced homocysteine-thiolactonase (BLH), may play a significant role in Alzheimer's disease. Could boosting its activity offer a new preventative strategy?"

Alzheimer's disease (AD) is a growing global health crisis, affecting millions and placing immense strain on healthcare systems and families. While significant research efforts are underway, effective preventative measures and treatments remain elusive. One promising area of investigation focuses on the role of homocysteine (Hcy), an amino acid in the blood, and its connection to brain health.

Elevated levels of homocysteine have been identified as a risk factor for AD. However, the relationship is complex. The body has mechanisms to manage Hcy levels, one of which involves an enzyme called bleomycin hydrolase (BLH). BLH has multiple functions, including homocysteine-thiolactonase (HTase) activity. This activity is critical to protect cells, removing a toxic byproduct of Hcy metabolism. This raises a critical question: Could BLH activity influence the development or progression of AD?

Recent research has explored this connection, measuring BLH activity in brain tissue from AD patients and healthy controls. The findings reveal a potential link between reduced BLH activity and AD, opening new avenues for understanding and potentially combating this devastating disease.

The Enzyme Connection: What Does BLH Do in the Brain?

Bleomycin hydrolase (BLH) is a ubiquitous enzyme found in nearly all human tissues, including the brain. It's a thiol-dependent aminopeptidase, which means it relies on sulfur-containing compounds to function and breaks down proteins by cleaving amino acids. While its exact function is still being researched, scientists know BLH plays a vital role in several cellular processes:

BLH acts as a 'detoxifier' for a harmful compound called homocysteine-thiolactone. This compound forms when homocysteine, a natural amino acid, is incorrectly processed during protein production. Homocysteine-thiolactone can damage proteins and disrupt cellular function. BLH neutralizes this threat, preventing protein damage.

Protein Recycling: BLH participates in the breakdown and recycling of proteins, a fundamental process for maintaining healthy cells.
Amino Acid Release: In the skin, BLH helps liberate moisturizing amino acids, showcasing its diverse roles across different tissues.
Amyloid Precursor Processing: Intriguingly, BLH has been shown to interact with the amyloid-beta protein precursor, a key player in Alzheimer's disease, suggesting a direct link to AD pathology.

Given these diverse functions, researchers hypothesized that BLH activity might be altered in AD patients. Specifically, they investigated two key activities of BLH: HTase (homocysteine-thiolactonase) and APase (aminopeptidase) in brain tissue samples.

A Promising Direction for Future Research

This research offers valuable insights into the role of BLH in Alzheimer's disease. The finding that reduced BLH activity correlates with increased N-Hcy-protein suggests a potential target for future therapies. Further studies are needed to confirm these findings in larger populations and to explore the mechanisms by which BLH activity is regulated in the brain. If scientists can find ways to boost BLH activity, it could offer a novel approach to prevent or slow the progression of Alzheimer's disease, bringing hope to millions affected by this devastating condition.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3233/jad-2010-1311, Alternate LINK

Title: Reduced Homocysteine-Thiolactonase Activity In Alzheimer'S Disease

Subject: Psychiatry and Mental health

Journal: Journal of Alzheimer's Disease

Publisher: IOS Press

Authors: Joanna Suszynska, Joanna Tisonczyk, Hyoung-Gon Lee, Mark A. Smith, Hieronim Jakubowski

Published: 2010-03-11

Everything You Need To Know

What is the connection between homocysteine and Alzheimer's disease?

Elevated levels of homocysteine (Hcy), an amino acid in the blood, are recognized as a risk factor for Alzheimer's disease (AD). The body naturally manages Hcy levels, but when this process goes awry, it can contribute to AD. BLH, specifically its homocysteine-thiolactonase (HTase) activity, plays a crucial role in mitigating the harmful effects of Hcy. Reduced BLH activity can lead to increased levels of a toxic byproduct of Hcy metabolism, potentially damaging proteins and disrupting cellular function, which is linked to the progression of AD.

How does the enzyme BLH protect the brain?

Bleomycin hydrolase (BLH) is a critical enzyme with multiple functions, including homocysteine-thiolactonase (HTase) activity. This particular activity is vital because it acts as a 'detoxifier,' neutralizing homocysteine-thiolactone, a harmful byproduct of homocysteine (Hcy) metabolism. This prevents protein damage and cellular dysfunction. Additionally, BLH participates in protein recycling and interacts with the amyloid-beta protein precursor, which is another key player in Alzheimer's disease. These functions collectively highlight BLH's protective role in maintaining brain health.

What are the different functions of Bleomycin hydrolase (BLH) in the body?

Bleomycin hydrolase (BLH) is a versatile enzyme involved in several cellular processes. Primarily, it acts as a homocysteine-thiolactonase (HTase), neutralizing the toxic homocysteine-thiolactone. Beyond this critical function, BLH is involved in protein recycling and the release of moisturizing amino acids in the skin. Furthermore, it interacts with the amyloid-beta protein precursor, a key player in Alzheimer's disease, suggesting a link to AD pathology. These diverse roles emphasize the importance of BLH in maintaining cellular health across different tissues.

Why is the research on BLH and its connection to Alzheimer's disease so important?

The research linking reduced BLH activity to Alzheimer's disease (AD) is significant because it opens new avenues for understanding and potentially combating this devastating illness. By measuring BLH activity in brain tissue, scientists have identified a potential target for future therapies. This finding suggests that boosting BLH activity could offer a novel approach to prevent or slow the progression of AD. Further studies are needed to confirm these findings and explore how BLH activity is regulated in the brain. If successful, this could bring hope to millions affected by AD.

Can increasing BLH activity be a potential treatment for Alzheimer's disease? And how?

Yes, increasing BLH activity holds promise as a potential treatment strategy for Alzheimer's disease (AD). Research indicates that reduced BLH activity correlates with increased levels of harmful byproducts from homocysteine (Hcy) metabolism, which can damage proteins and disrupt cellular function, which is linked to AD. The central function of BLH in this context is its homocysteine-thiolactonase (HTase) activity. If scientists can find ways to boost BLH activity, particularly its HTase function, it could help neutralize these harmful byproducts, potentially preventing or slowing the progression of AD. Further research is needed to understand the precise mechanisms by which BLH activity is regulated in the brain and to develop effective methods for increasing its activity.