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 ...
07/10/2026
Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Zixi, a leader in live video delivery and workflow orchestration, and Comcast Technology Solutions (CTS) today announced a strategic new integration to deliver ...
16/07/2026
Blackmagic Design Cameras Capture Immersive Flight for New Cirrus App
Brie Clayton July 15, 2026
0 Comments
Leader in Personal Aviation taps URSA Cin...
16/07/2026
XenData Announces LTO Archive Appliances with both File and S3 Object Storage In...
16/07/2026
Together the semi-finals had a combined reach of 1.98 million unique individuals...
15/07/2026
The 2026 FIFA World Cup is a big deal for DAZN, which has distribution rights in three markets: Italy, Spain, and Japan. Each requires a different editorial app...
15/07/2026
As sports-media organizations manage rapidly growing content libraries and incre...
15/07/2026
HBS director of digital Johannes Franken talks SVG Europe through the operation built to serve FIFA World Cup 2026 rights holders remotely from Stratford, east ...
15/07/2026
IBC has unveiled the conference program for IBC2026, with this year's event ...
15/07/2026
Software-defined wideband RF platform supports 96-kHz monitoring, streamlined fr...
15/07/2026
New AI-powered module enables broadcasters and content owners to extract dialogu...
15/07/2026
Weeklong gathering at EBU headquarters will test new IPMX capabilities and expand certified product ecosystem...
15/07/2026
Force Tech has announced the appointment of Bryan Adams, CTS, as Vice President of Integration. Adams will oversee AV and broadcast integration project delivery...
15/07/2026
USA Sports has announced an exclusive English-language agreement with the Bundes...
15/07/2026
ITV Sport's FIFA World Cup 2026 coverage has been produced from one of the m...
15/07/2026
Program will provide professional camera kits, training, and technical support to participating local newsrooms...
15/07/2026
San Francisco church becomes first U.S. deployment of the 2 M/E production switcher...
15/07/2026
Former ESPN and NFL Network executive to advise startup league on media, distribution, technology, and fan engagement...
15/07/2026
The Houston-based RSN is the live-game home of the Astros and Rockets...
15/07/2026
Launched alongside new FreqSoft installer
Designed to bridge the gap between hardware and software, Freqport's FreqInOut FO1 unit provides a simple way ...
15/07/2026
Save up to 55% on software until 23 July 2026
Expressive E have just launched their Summer Offer sale, with discounts of up to 55% now applied across their ...
15/07/2026
Real-time stem-separation tool updated
zplane have recently released a new and improved version of their real-time stem-separation plug-in which they say ma...
15/07/2026
A new benchmark in bass enhancement
Described as a new benchmark in bass enhancement , Baby Audio's latest release has been designed to augment the lo...
15/07/2026
DMC Production's AR 1 and AR 2 units reverse the conventional OB workflow, keeping all production-critical processing at the venue while operators work remo...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
GigaCloud, a leading Ukrainian cloud service provider, and Cubbit, the first geo-distributed cloud storage enabler, today announced a new Business Alliance Part...
15/07/2026
SMPTE, the global society for media professionals, technologists, and engineers, has announced the launch of the SMPTE 110th Anniversary Campaign, a fundraising...
15/07/2026
Studio Technologies, a leading manufacturer of high-quality audio, video, and fiber-optic solutions, unveils the new StudioComm Model 762 Stereo Level Control, ...
15/07/2026
COW Jobs: Producer, Virtual Events - Hybrid, Full Time, Salaried
Brie Clayton July 15, 2026
0 Comments
Producer, Virtual Events (Hybrid | Full-time | ...
15/07/2026
Brazilian media organization builds nationwide CDN with Broadpeak's high-performance software for low-latency streaming and new content distribution service...
15/07/2026
DHD announces a new utility designed to increase the efficiency of its audio mixing systems during initial installation and subsequent configuration.
Anyone w...
15/07/2026
BCNEXXT Brings Next-Generation Vipe to IBC2026, Breaking the 1:1 Channel-to-Server Ratio New innovations liberate broadcasters from legacy playout infrastructur...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
General-purpose robots and autonomous machines are moving from research labs to ...
15/07/2026
Wednesday 15 July 2026
Screeners and press pack now available: Gomorrah: The Or...
15/07/2026
Trinity's Treasures features Ruth Negga, Eleanor McEvoy, and David Norris, a...
15/07/2026
Join geographer Dr Susan Hegarty, Engineer Tim Joyce and Architect Orla Murphy a...
15/07/2026
Home to leading manufacturers, robotics pioneers, infrastructure builders and iconic gaming companies, of course, Japan is one of the world's centers of AI ...
14/07/2026
South end zone videoboard, cloud-based control system will be ready for 2026 football season...
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. 
