Hidden network of enzymes accounts for loss of brain synapses in Alzheimer's The discovery of abnormal chemical reactions may lead to novel targets for drugs that treat neurodegenerative diseases.
December 03, 2020
LA JOLLA, CA A new study on Alzheimer's disease by Scripps Research scientists has revealed a previously unknown biochemical cascade in the brain that leads to the destruction of synapses, the connections between nerve cells that are responsible for memory and cognition.
The findings present a fresh angle for discovering drugs that treat Alzheimer's disease, which affects roughly 50 million people worldwide. The study, led by Scripps Research Professor and Step Family Foundation Endowed Chair Stuart Lipton, MD, PhD, appears in the journal Science.
This newly-discovered series of abnormal chemical events, termed protein transnitrosylation reactions, contribute to synapse loss, the main driver of memory loss and cognitive decline in Alzheimer's.
Lipton, who is also a clinical neurologist, explains that most recent attempts to develop Alzheimer's treatments have targeted the sticky protein known as beta amyloid that accumulates in the brain of patients, disrupting cell communication and causing inflammation. However, for a variety of reasons, these attempts have failed in clinical trials.
This work gives us new hope for better therapeutic targets, as the reactions we discovered are downstream of amyloid action, Lipton says. We've opened up a whole new avenue for drug development.
Lipton is no stranger to drug development for Alzheimer's and Parkinson's diseases. Drugs developed in and patented by his laboratory have led to four FDA-approved medicines for these diseases, including the widely prescribed drug, memantine (Namenda ). Much better drugs are needed, however, Lipton says.
A chemistry success story
In the new study, Lipton and his team used physical chemistry techniques to quantify how electrons participate in chemical reactions, as they suspected unknown processes may be taking place in the brain. Through this, they uncovered the entirely new series of biochemical events in nerve cells affected by Alzheimer's.
They found that small clumps of beta amyloid protein trigger excessive neuron activity and inflammation, leading to the destructive series of transnitrosylation reactions.
The process begins with excessive levels of nitrogen (N) and oxygen (O) atoms joining together as an NO group, which is then transferred to a protein building block called cysteine to regulate the activity of the protein. A series of these aberrant protein reactions cuts off energy to the brain's nerve cells by disrupting their mitochondria organelles that generate power for the cell's biochemical reactions. This eventually leads to loss of synapses connecting the nerve cells.
We were able to show that these reactions occur in brains of Alzheimer's patients, and when we prevented these reactions in the brains of animal models of the disease, we protected the synapses, Lipton says. Our findings suggest that it may be possible to intercede to reverse synapse damage in spite of plaques and tangles, he added, referring to plaques of beta amyloid and tangles of misfolded tau protein, both of which are characteristic of Alzheimer's disease.
He notes that while normal levels of NO foster memory and learning, excessive levels can build up as we age and become harmful to synapses.
With this new knowledge, we may be able to restore synaptic connections in Alzheimer's patients after extensive plaques and tangles have formed in their brains, adds Tomohiro Nakamura, PhD, senior staff scientist in the Lipton laboratory group and first author of the study.
Revealing secret connections
Lipton says that one of the team's most incredible findings was that the three enzymes discovered to pass NO to each other along a concerted chain of events, resulting in energy failure, were previously not thought to be even remotely related to one another. Each of the enzymes is important in its own right in a completely disparate normal biochemical pathway, and yet they interact under disease conditions in a novel manner to trigger intense neuronal stress and synapse damage.
This type of hidden or ghost' pathway may only become evident under disease conditions and may represent an important fundamental tenet of why we did not understand the disease process previously, Lipton says. If we do not know about a pathway, scientists cannot study its contribution to disease or develop drugs to treat it.
While many molecular biochemical pathways have been discovered, an over-reliance on this existing body of evidence can actually impede discovery of disease processes, he adds.
Hence, the most important aspect of the work is that we have to be on our guard to look for new pathways and new relationships of existing enzymes in order to understand and treat neurodegenerative disorders such as Alzheimer's, Lipton says.
In addition to Nakamura and Lipton, other authors of Non-canonical transnitrosylation network contributes to synapse loss in Alzheimer's disease, include Chang-ki Oh, Xu Zhang, Kevin Lopez, Amanda Deal, Henry Scott, Lujian Liao and John R. Yates III from Scripps Research; and Daniel Gibbs, Brian Spencer, Robert Rissman and Eliezer Masliah from the University of California, San Diego.
The work was funded by the National Institutes of Health and philanthropic support.
Neurological Disorders Molecular and Cellular Biology Lipton, Stuart
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
02/05/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
01/05/2026
January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...
06/04/2026
Michigan legends bring a new voice to the broadcast as TNT Sports and CBS Sports...
06/04/2026
From high school sports all the way up to the major leagues, building high-quali...
06/04/2026
Quickplay, an AI company for the media and entertainment industry, has been accepted into the Advanced tier of the TwelveLabs Ecosystem Partner Program. Quickpl...
06/04/2026
Grass Valley has announced the Future Playmakers Program, a global initiative to...
06/04/2026
El l der de operaciones impulsa la producci n en estudio mientras encuentra insp...
06/04/2026
The ops leader helps lead the charge in studio for the Spanish-language broadcas...
06/04/2026
Behind The Mic provides a roundup of recent news regarding on-air talent, includ...
06/04/2026
The National Hockey League (NHL), in partnership with Verizon and the New Jersey Devils, today announced the opening of the NHL Innovation Lab powered by Verizo...
06/04/2026
Rock League, a new professional curling league, has announced that ESPN+ will stream its inaugural 2026 season for fans in the United States. The first Rock Lea...
06/04/2026
Advanced Systems Group has announced the appointment of Andrea (Andy) Cummis as Vice President of Systems Design and Engineering. In this role, she will lead de...
06/04/2026
Backed by Bolt Ventures, the venture brings Bryson DeChambeau, Grant Horvat, and...
06/04/2026
With this environment we can start that collaboration even earlier because we ca...
06/04/2026
Like the immortal lives of vampires, some stories never really end. That's t...
06/04/2026
As podcasting continues to evolve, growth increasingly means building beyond aud...
06/04/2026
Multiband dynamics plug-in enhanced
California-based developer FSK Audio have released a significant update for their innovative multiband dynamics processo...
06/04/2026
Share official & user-created full-rig presets
IK Multimedia's latest TONEX update makes it possible for users of the popular amp and effects modelling ...
06/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/04/2026
Dalet Showcases Dalia Agentic AI and End-to-End Media Workflows at NAB Show 2026
Brie Clayton April 6, 2026
0 Comments
Dalet, a leading technology and...
06/04/2026
OpenDrives Shows Off Sports Expertise in Sports Business Hub located in NAB Show...
06/04/2026
Proton to Demonstrate 3D Application at NAB 2026
Brie Clayton April 6, 2026
0 Comments
Yet further creative potential unleashed through innovation in ...
06/04/2026
Autoscript Highlights Voice-Driven Prompting and PTZ Solutions at NAB 2026
Brie Clayton April 6, 2026
0 Comments
Experience Autoscript Voice, PTZ prom...
06/04/2026
Mediaproxy Highlights Significant Enhancements to its LogServer suite at NAB Sho...
06/04/2026
Back to All News
Netflix Expands Kids Entertainment Lineup With Playground App ...
05/04/2026
Tackles all reported bugs!
SoundBridge have just announced the launch of a new update that introduces a couple of minor changes to their remote collaboratio...
04/04/2026
The University of Arizona's Men's Basketball team has only loss twice th...
04/04/2026
1080p HDR arrives, a new generation of storytelling tools takes center stage, an...
04/04/2026
Michigan legends bring a new voice to the broadcast as TNT Sports and CBS Sports...
04/04/2026
Faster, cleaner and more intuitive than ever
The control software for Flock Audio's digitally controlled patchbay systems has just been treated to an up...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
DHD Introduces AI-Based Audio Noise Reduction to XD3 IP Core
Brie Clayton April 3, 2026
0 Comments
The accompanying image shows the rear panel of the ...
04/04/2026
Macnica Redefines ST 2110 Flexibility with Two Speeds on One Card
Brie Clayton April 3, 2026
0 Comments
New for NAB Show 2026, MEP100 SmartNIC now sup...
04/04/2026
Unified Media Workflows for Story-Centric Production
Brie Clayton April 3, 2026
0 Comments
Framelight X unifies field capture, editing and publishing ...
03/04/2026
Michigan's Fab Five will reunite for an alternate presentation of the Mich...
03/04/2026
Avid will exhibit at NAB Show 2026 (April 18-22, Booth N2226, Las Vegas Convention Center), demonstrating its Content Core platform and new AI-driven workflow c...
03/04/2026
Mark Roberts Motion Control (MRMC) has announced the appointment of Nick Barthee as Chief Operating Officer.
The announcement follows MRMC's transition fro...
03/04/2026
Interra Systems has announced that Elite Media Technologies has selected its BATON file-based QC solution for media workflows. Elite Media Technologies speciali...
03/04/2026
Ateme has announced that Moldtelecom has deployed Ateme technologies across its streaming workflow, covering encoding, delivery, operations, and analytics.
Mol...
03/04/2026
Grass Valley will demonstrate Framelight X, its content management platform, at NAB Show 2026. The platform connects capture, ingest, editing, and publishing in...
03/04/2026
Encompass Digital Media and Techex have announced a cloud-native Master Control ...
03/04/2026
Live Vertical Video automatically track the action on the court via AI technology and delivers a fully optimized, 9 16 live feed for viewers...
03/04/2026
As the Illini make their first trip to college basketball's biggest stage si...
Hidden network of enzymes accounts for loss of brain synapses in Alzheimer's The discovery of abnormal chemical reactions may lead to novel targets for drugs that treat neurodegenerative diseases. 
