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...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Liberty University on why broadcast technology isn't just a technical invest...
08/05/2026
COW Jobs: UGC, On-Camera Video Content
Brie Clayton May 7, 2026
0 Comments
UGC, On-Camera Video Content
April 17, 2026Documentary Editor - US,......
07/05/2026
Journalists reporting on Sudan are working in one of the most complex and fast-m...
07/05/2026
Multi-year partnership positions Victory+ as a free home for Dallas Cowboys orig...
07/05/2026
From sideline reporting to directing and producing, the talented sophomore is building a well-rounded foundation for a career in live sports production
In the ...
07/05/2026
Cobalt Digital has received two Future Best of Show awards at NAB Show 2026. The COBALT blueCORE platform was recognized by TV Tech, and the COBALT PACIFIC ULL-...
07/05/2026
ESPN analyst Mina Kimes will host the televised semifinals and finals of the 202...
07/05/2026
Bitmovin has announced that MUBI, the global film streaming platform, has selected Bitmovin as its cloud VOD encoding partner. Bitmovin's encoding infrastru...
07/05/2026
NBCUniversal Telemundo Enterprises and the U.S. Soccer Federation have announced...
07/05/2026
Angel City Football Club (ACFC) and Victory have announced a regional broadcast partnership bringing live match coverage to fans across the greater Los Angeles...
07/05/2026
Spiideo has announced the launch of AI Highlights inside Spiideo Play, its automated sports production platform. AI Highlights combines video, event data, audio...
07/05/2026
Leostream Corporation has announced a unified remote access ecosystem for high-p...
07/05/2026
The Atlanta Dream has partnered with Victory to stream all locally broadcast Dream games for free, expanding the team's digital distribution strategy and g...
07/05/2026
Riedel Communications has announced the appointment of Marc Engroff as Chief Fin...
07/05/2026
SES and ARD, Germany's largest public broadcasting network, have announced a long-term extension of their satellite distribution partnership through 2039. U...
07/05/2026
UpLight Technologies delivers a flexible video and lighting system for a new televised sportLaunching the Pro Cheer League required more than creating a compell...
07/05/2026
Full Day Productions and GSE Worldwide have announced Spikes Under the Lights, a...
07/05/2026
Seit dem Start im Jahr 2023 hat DJ (Beta) das personalisierte H rerlebnis von 94...
07/05/2026
Da quando stata presentata nel 2023, DJ (beta) ha aiutato a definire un'esperienza d'ascolto pi personalizzata per 94 milioni di utenti Spotify Premi...
07/05/2026
Since launching in 2023, DJ (beta) has helped shape a more personalized listenin...
07/05/2026
Desde o lan amento em 2023, o DJ (beta) j ajudou a deixar a experi ncia de ouvi...
07/05/2026
From our earliest days, Spotify has been built on a simple principle: Great audio should be easy to reach. It's what's driven us to expand from music to...
07/05/2026
Asian and Pacific Islander artists continue to shape the global soundscape, pushing creative boundaries and connecting with fans worldwide. This Asian & Pacific...
07/05/2026
Company announce long-requested choir instrument
In the latest expansion of their Symphonic Elements series, UJAM have introduced an all-new vocal instrumen...
07/05/2026
Modular-inspired sound generation with digital control
Buchla have introduced Ziggy, a new compact synthesizer built around the company's complex oscill...
07/05/2026
Combines analogue voices with digital synthesis and sequencing
Polyend have announced Drums, a new hybrid analogue and digital drum machine that combines sy...
07/05/2026
Control surface now officially supports four DAWs
When Nektar launched the Panorama CS12 control surface, it worked exclusively with Apple's Logic Pro, ...
07/05/2026
In the first quarter 2026, SGL Carbon generated consolidated sales of 184.5 million, which was 49.8 million, or 21.3%, lower than in the prior year (Q1 2025: ...
07/05/2026
Rohde & Schwarz and Greenerwave achieve precise and fast ESA antenna characteriz...
07/05/2026
Two multi-role L3Harris products - the Red Wolf launched effects vehicle and SK...
07/05/2026
L3Harris will be developing key features of a secure and resilient digital infra...
07/05/2026
Alysa Liu and Shohei Ohtani Help Drive Viewership as 91 of the Top 100 Broadcast...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Cobalt Digital Wins Two Future Best of Show Awards at 2026 NAB Show
Manufacturer Recognized by TV Tech and TVBEurope for Innovation in signal processing
Cobal...
07/05/2026
Software and hardware platforms, AI power and user-friendliness on show...
07/05/2026
Intinor will demonstrate its latest technical enhancements for the Direkt series at BroadcastAsia 2026. With a continued focus on reliable contribution and remo...
07/05/2026
Bitmovin has announced that MUBI has chosen Bitmovin as its cloud VOD encoding partner, replacing MUBI's legacy on premises encoding setup to improve scalab...
07/05/2026
Meet Graduates from Berklees Class of 2026 Members of this years graduating class reflect on their proudest moments at Berklee and look ahead to whats next.
...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
At BroadcastAsia 2026, Interra Systems will demonstrate its latest innovations in automated quality control (QC), real-time monitoring, and captioning. The comp...
07/05/2026
At this year's Broadcast Asia, PlayBox Neo is set to unveil recent innovations across its PlayBox Neo Suite and integrated range of broadcast media solution...
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. 
