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 ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
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...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Zero in on one that says yes (and no)
Andy Marken May 29, 2026
0 Comments
Hero image courtesy of Deposit Photos
For content creators the most difficu...
29/05/2026
With InfoComm 2026 just weeks away, NDI is giving attendees plenty of reasons to...
29/05/2026
Reaffirming a partnership that has defined Canadian sports broadcasting since 19...
29/05/2026
Mobile/tablet is No. 2 device for watching TV, suggesting that the sports-production industry needs to take another look at the format
Ring Digital's Sprin...
29/05/2026
Berliner Ensemble, one of Berlin's five major theater companies, has expande...
29/05/2026
Solid State Logic will showcase its new compact, fly-away TCA Tour audio product...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, passed away last month on April 12 ...
29/05/2026
Paramount+ will be the English-language U.S. home for Barclays Women's Super...
29/05/2026
Further strengthening its virtualisation strategy to fully support broadcasters ...
29/05/2026
Swiss broadcaster Canal Alpha has deployed Harmonic's award-winning, software-based XOS Advanced Media Processor to modernize playout operations across cant...
29/05/2026
PTZOptics will showcase a new generation of intelligent video workflows at InfoComm 2026, June 17-19, Las Vegas. Visitors to booth N8227 will see how PTZOptics ...
29/05/2026
Arizona's Family has launched the Arizona's Family Sports (AZFS) streaming app, a new direct-to-consumer destination for live, local sports. The app is ...
29/05/2026
Starting in 2027, DAZN will be the exclusive home of The Canadian Football Leagu...
29/05/2026
Comcast Business has detailed the advanced network infrastructure it has deploye...
29/05/2026
In two-day event, leaders from academia and industry explored solutions to chall...
29/05/2026
The Basketball Tournament (TBT), now entering their 13th year of competition, ha...
29/05/2026
Roku has launched FOX One as a Premium Subscription on The Roku Channel in the U.S. Roku customers can now subscribe to FOX One using their Roku account for liv...
29/05/2026
In its sixth year, the broadcaster's coverage has become a global brand and ...
29/05/2026
Ratings Roundup is a rundown of recent ratings news and is derived from press re...
29/05/2026
The days are getting longer, the temperatures are rising, and playlists are filling up for the season. With summer around the corner, Spotify's global edito...
29/05/2026
New retro-inspired MPC announced
There are few devices that have gained the status held by Akai Pro's MPC range, and in recent years, the company have s...
29/05/2026
Save up to 30 on acclaimed titles
Following a successful launch at Superbooth 2026, Bjooks have revealed that they will be continuing the Kickstarter campa...
29/05/2026
Binaural monitoring application improved
Genelec have just released an update that brings some powerful new features to their HRTF-based binaural headphone ...
29/05/2026
6 June 2026 at SAE Institute, London, UK
IMSTA FESTA 2026 is almost upon us, with some of the biggest names in pro-audio set to descend upon SAE Institute i...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, died April 12, 2026, at his home in...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Comparing 5 AI Video Enhancers for Restoring Old Video Quality
Kate Luvis May 29, 2026
0 Comments
Digitizing VHS, MiniDV, and other legacy formats doe...
29/05/2026
Studio Hamburg Builds New Post Pipeline with DaVinci Resolve Studio
Brie Clayton May 29, 2026
0 Comments
Workflow replaces a patchwork of legacy tools...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
At the Intersection of Music and Dance, an Epic Collaboration Boston Conservatory musicians and dancers found creative parallels in their recent performance o...
29/05/2026
GLOOKAST LAUNCHES CINNAFILM TACHYON PLUGIN FOR MEDIA PRODUCER AND MEDIA SERVICES
This release first appeared here.
Visit our Tachyon product page or contact...
29/05/2026
May 29 2026, 09:00 (PDT) Dolby and rednote Bring More Immersive Storytelling to...
29/05/2026
Something fundamental has shifted in how people consume media. Audiences aren't abandoning television or radio content; they're just expanding how, wher...
29/05/2026
Youtube exclusive special drops today
Watch now
UKTV today announces another e...
29/05/2026
Back to All News
The Official Trailer of Physical 100 Italy, on Netflix From Se...
29/05/2026
Genelec announces V2.1 for Aural ID binaural headphone monitoring application posted: 29/05/2026
Aural ID 2.1 enhances binaural monitoring for stereo and ...
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. 
