Snake Venom Combating Alzheimer's

When we first think of snake venom, our first thoughts often lead to negative associations with poisons and danger. However, the surprising discovery by a team of researchers in Australia has challenged this common perception. The team recently identified a unique molecule within snake venom that holds a promising value to the medical industry. This groundbreaking discovery could play a critical role in combating Alzheimer’s disease, one of the top ten leading causes of death worldwide. 

While Alzheimer’s disease has been around for over a century, it remains a medical condition without a permanent cure to date. This is because current medications typically focus on managing its symptoms, such as slowing the process of memory loss and preserving individuals’ abilities to perform daily tasks independently, instead of addressing the underlying causes of the disease. To understand how the molecule in snake venom serves as a therapeutic potential, it is important to first recognize the key components and functions of a healthy brain and how they are disrupted in Alzheimer’s patients. 

A Healthy Brain vs. Alzheimer’s Brain 

On average, a human brain consists of around 90 billion neurons and over 100 trillion synaptic connections, or gaps between these nerve cells through which chemicals called neurotransmitters can transfer from one to another. These synapses allow for communication between neighboring neurons, helping our brains perceive, process, and direct different actions that are necessary for life. In a healthy brain, proteins called amyloid precursor proteins (APP), which are important for helping neurons develop and communicate with each other, are normally processed to produce fragments known as amyloids. Under normal conditions, these protein fragments are degraded from the brain effectively by enzymes. However, in Alzheimer’s disease patients, the fragments, with amyloid beta being the most toxic form, remain and form aggregates called amyloid plaques. These plaques threaten the functions of neurons by accumulating between synapses, preventing communication, promoting inflammation, and even leading to nerve cell death. Preventing the formation of amyloid plaques, a hallmark of Alzheimer’s disease, is exactly where the molecule snake venom metalloproteinase (SVMP) comes in, as it may be able to stop the formation of amyloid beta fragments and their ability to accumulate to dangerous levels.

SVMP - The Potential Treatment 

For decades, it has been known that SVMP serves as around 30% or more of the total protein in most viperid venom; however, its connections to preventing amyloid beta formation have just been recently brought to light. By isolating SVMP from the rest of its viperid venom counterparts, scientists surprisingly discovered that it is closely similar, both in structure and function, to a family of proteins that naturally prevent amyloid beta formation in mammals. This family is known as a disintegrin and metalloproteinase (ADAM) proteins, and they are critical for their roles in processing APP in mammals to produce non-harmful forms of amyloids instead of the toxic amyloid beta. While SVMPs are mainly found in snakes and ADAMs are present in mammals, further analysis showed that they share similar parts, called domains, that help them recognize and cut other proteins into smaller pieces, a process called protein cleavage. A key part that is present in both molecules contains a metal ion (usually zinc), that is critical for the cutting action, analogous to using a pair of scissors to cut a ribbon into smaller pieces. These similarities prompted scientists to hypothesize whether SVMPs might have a role in the cleavage of APP into non-harmful forms of amyloid instead of amyloid beta, and current research efforts demonstrate that they are likely to be on the right track.

Promising Research and Experimental Studies 

In a study conducted by the University of Tokyo and Tohoku University, the researchers purified nine types of SVMPs from a species of pit viper and combined them to create a “snake venom cocktail”. Using this cocktail, they mixed it with a human cell culture medium and found that the venom proteins decreased the production of amyloid beta by acting at the same cutting sites as certain ADAM proteins. In addition, they also observed that the venom cocktail can cut and break down amyloid-beta into smaller, harmless molecules, further lessening its threat in promoting Alzheimer’s disease. While the exact cutting mechanisms are not identical between SVMPs and ADAMs, and additional efforts are needed to determine the optimal dosage of the snake venom cocktail, these promising results demonstrate its potential as a novel approach to reducing amyloid beta levels and combating Alzheimer’s disease. 

With more bioengineering efforts, we can be more hopeful every day that SVMPS may one day be engineered to function effectively in human bodies. Teams of researchers around the world are actively exploring how these proteins can be adapted for safe and controlled use while targeting amyloid beta accumulation in human brains. Even though Alzheimer’s disease has remained untreatable for the past century, the continuous advancements in research bring us closer to the possibility of breakthroughs that could help pave the way for more successful treatments for the disease. 

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Written by Dory Meng 

References 

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molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-6-27#:~:text =The%20amyloid%20precursor%20protein%20. 

"Conquering Alzheimer's disease with poison: Tohoku University finds that enzyme from venom of the snake Protobothrops flavoviridis degrades dementia-causing substance." ScienceJapan, sj.jst.go.jp/news/202312/n1205-01p.html. 

"A Metalloproteinase Cocktail from the Venom of Protobothrops Flavoviridis Cleaves Amyloid Beta Peptides at the α-Cleavage Site." Toxins, pubmed.ncbi.nlm.nih.gov/37624257/. "Snake Venom May Hold Key to Breaking down Plaques That Cause Alzheimer's Disease - Monash University." Monash University, 

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